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THERAPEUTICS: 

ITS 

PRINCIPLES AND PRACTICE 



BY 

HORATIO C. WOOD, M.D., LL.D. 

(Lafayette, Yale, Pennsylvania) 

EMERITUS PROFESSOR OF MATERIA MEDICA AND THERAPEUTICS IN THE UNIVERSITY OF PENNSYLVANIA; 
MRMRER OF THE NATIONAL ACADEMY OF SCIENCE 



THOROUGHLY REVISED AND REWRITTEN 

It 

BY 

HORATIO C. WOOD, Jr., M.D. 

ASSOCIATE PROFESSOR OP PHARMACOLOGY IN THE UNIVERSITY OF PENNSYLVANIA; ASSISTANT 
PHYSICIAN TO THE PHILADELPHIA GENERAL HOSPITAL 



FOURTEENTH EDITION 




PHILADELPHIA y LONDON 

J. B. LIPPINCOTT COMPANY 



LlBHARY Ot CttNiJRESS 
|M oopies IMcvitcf 

St, 16 »*>* 

■>U\i> A AAC. Nu 

j5py S. 



ed, according to Act of Congress, in the year 1875, by 
J. B. LIPPINCOTT & CO., 
In the Office of the Librarian of Congress, at Washington. 



Copyright, 1S79, 1882, 
« 'opyright, 1885 
f opyright, 1888. 
Copyright, 1891 
i opyright, isiH 
Copyright, 1897 
i opyright, moo 
i opyright, 1905, 
Copyright, 1906, 
t opyright, 1907 
Copyright, 1908 



and 18S3, by J. B. Lippincott & Co. 
, by J. B. Lippincott Company. 

by J. B. Ljppincott Company. 

by J. B. Lippincott Company. 

by J. B. Lippincott Company. 

by J. B. Lippincott Company. 
,byJ. B. Lippincott Company. 

bj I. B. LrpPTNi 01 r Company. 

by J. B. Lippincott company. 
, by J. B. LlPPINl ott Company. 
. by J. K. Lippincott Company. 



Klirtrotyptd and printed by J. B. Lippincott Company 
IT"' "' • Philadelphia. V. 8. A. 



DR. GEORGE B. WOOD, LL.D., 

THIS BOOK 



IS DEDICATED BY THE AUTHOR, HIS NEPHEW, 

AS A TOKEN OF RESPECT AND 

AFFECTION. 



PREFACE TO THE FOURTEENTH EDITION 



The alterations in the present edition of this treatise are more 
extensive than those in any previous edition for many years. Many 
of these changes are the result of an effort to make the book more 
available as a student's text-book without lessening its value as a 
work of reference for the practitioner or scientist. 

The fundamental facts which the undergraduate student should 
be required to know are printed in large type, while the discussion 
of the more intricate details of pharmacology and the therapeutic 
data of less importance are printed in smaller type. The descrip- 
tions of the physical characteristics of the drugs at the beginning 
of each article have been carefully revised, and enlarged where 
deemed necessary, so that, although the book does not pretend to 
give a detailed treatise on materia medica, it is believed that it con- 
tains the facts on this subject which the practitioner of medicine 
should know. 

Besides the more systematic arrangement of the subject-matter 
and the changes above noted a considerable amount of alteration 
has been required to keep the work abreast of the recent discoveries 
in the rapidly advancing science of pharmacology. The whole field 
of medical literature of the world has been sedulously gleaned and 
facts of therapeutic interest which have been found incorporated 
in the text. Especially notable changes, however, have been found 
necessary in the following portions of the work: 

The chapter on cathartics has been completely rewritten and the 
matter considered in a more orderly manner, which we believe will 
be of advantage alike to the student and practitioner of medicine. 

The chapter on diuretics has been remodelled to correspond to 
the latest views of the physiology and pharmacology of this subject, 
and more space given to the consideration of the effects of water 
on the system and the action of mineral salts on the flow of urine. 

Articles on opsonic therapy and on the ion theory have been 
added. Also a number of new illustrations have been introduced 
where it was thought that they would elucidate the text;, many 
of these are photographic reproductions of blood-pressure and 
respiratory curves from experiments made by the reviser. 

Continued ill health has prevented the original author of this trea- 
tise from taking any active part in the present edition and the entire 
labor has fallen on his son, Dr. Horatio C. Wood, Jr., who has been 
associated in the various revisions of the work for the past eight years. 



PREFACE TO THE FIRST EDITION 



At the present time, when the shelves of private and public 
libraries are groaning beneath their ever-increasing loads, when a 
thousand presses in every city send forth day and night their printed 
messages until the earth is filled with them, it seems almost presump- 
tuous for any one to offer new volumes to the world. Indeed, art is 
so long, life is so short, that every student has the right to demand 
of an author by what authority he doeth these things, and to challenge 
every memoir for its raison d'etre. This being so, it assuredly will not 
appear egotistical for the author to state that his voluntary task was 
first suggested by his own wants, and that to its performance he has 
brought the training, labor, and experience of years spent in the 
laboratory, the study, the class-room, and the hospital ward. 

There are a number of excellent treatises upon materia medica 
and therapeutics; yet in various attempts at original research, as 
well as in the ward and the lecture-room of the hospital, I have keenly 
felt the want of something more. There are many points of view 
from which a subject can be looked at; there are many paths by 
which it may be approached; and to me, other points of view, other 
modes of approach, have been far more enticing than those adopted in 
our standard treatises. 

The old and tried method in therapeutics is that of empiricism, 
or, if the term sounds harsh, of clinical experience. As stated by one 
of its most ardent supporters, the best possible development of this 
plan of investigation is to be found in a close and careful analysis of 
cases before and after the administration of a remedy, and, if the 
results be favorable, the continued use of the drug in similar cases. 
It is evident that this is not a new path, but a highway already worn 
with the eager but weary feet of the profession for two thousand years, 

That very much has been thus accomplished it were folly to deny. 
Leaving out of sight the growth of the last two decades, almost all of 
the current therapeutic knowledge has been gained in this way. 

Therapeutics developed in this manner cannot, however, rest upon 
a secure foundation. What to-day is believed is to-morrow to be cast 
aside, certainly has been the law of advancement, and seemingly must 
continue to be so. What has clinical therapeutics established perma- 
nently and indisputably? Scarcely anything beyond the primary facts 
that quinia will arrest an intermittent, that salts will purge, and that 
opium will quiet pain and lull to sleep. 

To established therapeutic facts the profession clings as with 
the heart and hand of one man,— clings with a desperation and 
unanimity whose intensity is the measure of the unsatisfied desire 



viii PREFACE TO THE FIRST EDITION 

for something fixed. Yet with what a Babel of discordant voices 
doee it celebrate its two thousand years of experience! 

This is so well known that it seems superfluous to cite examples 
of the therapeutic discord; and one only shall be mentioned, — 
namely, rheumatism. In this disease, bleeding, nitrate of potassium, 
quinine, mercurials, flying blisters, purgation, opium, the bromides, 
veratria, and a host of oilier remedies, all have their advocates clam- 
orous for a hearing; and above all the tumult are to be heard the 
trumpet-tones of a Chambers, "Wrap your patients in blankets and 
let them alone." 

Experience is said to be the mother of wisdom. Verily she has 
been in medicine rather a blind leader of the blind; and the history of 
medical progress is a history of men groping in the darkness, finding 
seeming gems of truth one after another, only in a few minutes to 
cast each back to the vast heap of forgotten baubles that in their day 
had also been mistaken for verities. In the past, there is scarcely a 
conceivable absurdity that men have not tested by experience and 
for a time found to be the thing desired; in the present, homoeopathy 
and other similar delusions are eagerly embraced and honestly 
believed in by men who rest their faith upon experience. 

Narrowing our gaze to the regular profession and to a few decades, 
what do we see? Experience teaching that not to bleed a man suffer- 
ing from pneumonia is to consign him to an unopened grave, and 
experience teaching that to bleed a man suffering from pneumonia is 
to consign him to a grave never opened by nature. Looking at the 
revolutions and contradictions of the past, — listening to the thera- 
peutic Babel of the present, — is it a wonder that men should take 
refuge in nihilism, and, like the lotus-eaters, dream that all alike is 
folly, — that rest and quiet and calm are the only human fruition? 

Since the profession has toiled so long and found so little, if further 
progress is to be made we must question the old methods and search 
out new ones, which haply may lead to more fruitful fields. In the 
ordinary affairs and business of life, when anything is to be accom- 
plished, the effort always is to discover what is to be done, and then 
what are the means at command. A primary knowledge of the end 
to be accomplished, and a secondary acquaintance with the instru- 
ments, are a necessity for successful human effort; and until the 
sway of this law is acknowledged by physicians, medicine can never 
rise from the position of an empirical art to the dignity of applied 
science. Until within a comparatively recent period, it has been 
impossible to comply with this law. But, through the advances made 
by the pathologists and by the students of the natural history of dis- 
. we are fast learning the methods in which nature brings the 
body back to health. When this is done, — when disease is thoroughly 
understood, — we shall have wrought out the first element of the 
problem, shall have complied with the first requirement of the law. 

It is scarcely within the province of a therapeutist, and certainly 
is not possible within the scope and limits of this work, to discuss at 



PREFACE TO THE FIRST EDITION ix 

length the natural history of disease; but it is allowable to point out 
evident indications for relief; and this I have done to a greater or less 
extent throughout the book. 

The work of the therapeutist is chiefly with the second portion of 
the law. Evidently, it is his especial province to find out what are 
the means at command, what the individual drugs in use do when 
put into a human system. It is seemingly self-evident that the 
physiological action of a remedy can never be made out by a study of 
its use in disease. Under all circumstances, the problem is one of the 
most complex with which the human mind has to grapple; and to 
introduce into this problem the new and ever-varying factors of the 
effect of disease and its natural vibrations on the system is to put the 
matter beyond human prescience. 

In spite, then, of Dr. Niemeyer's assertion that experiments made 
with medicaments upon the lower animals or upon healthy human 
beings have, as yet, been of no direct service to our means of treating 
disease, and that a continuation of such experiments gives no prospect 
of such service, it is certain that in these experiments is the only 
rational scientific groundwork for the treatment of disease. We must 
discover what influence a drug exerts when put into the body of a 
patient before we can use it rationally; and we can gain this coveted 
knowledge only in the method indicated. 

It has been strenuously objected, especially to experiments upon 
animals, that drugs do not act upon the lower creatures in the same 
manner as they do upon man. When I first commenced the studies 
whose outcome is the present volume, I was profoundly impressed 
with the truth of this oft-repeated assertion and with the difficulties 
which it put in the way. To-day I do not believe that, stated in its 
broad sense, it is true. Indeed, more strongly, I assert that it is not 
true; that, in the vast majority of cases, the actions of -drugs upon 
man and upon the lower animals are, though seemingly different, in 
reality similar; that the more knowledge we acquire the fewer excep- 
tions remain unexplained; and that the whole matter is in all prob- 
ability subject to laws whose development will greatly aid in our 
explanation of various obscure clinical phenomena. 

The general proofs of these assertions are sufficiently obvious, I 
think, in the following pages to render it unnecessary for me to dwell 
upon them at length here: moreover, if they be not so obvious to 
others as to myself, space is here wanting for a full discussion of the 
subject. I can only make a few general remarks, and point out some 
of what I believe to be the governing laws. 

In the first place, degree and quality are distinct things, and should 
not be confounded. Yet they frequently are; and because it requires 
as much morphia to kill a pigeon of a pound weight as to destroy a 
man, we are told that medicines act differently upon man and the 
lower animals. Evidently the conclusion is a non sequitur, and dif- 
ference of susceptibility is no proof of difference in the mode of impres- 
sion. A teaspoonful of Epsom salt may purge one man, while it may 



x PREFACE TO THE FIRST EDITION 

require ounces to affect another. Evidently there is a difference of 
susceptibility; but when the impression is once made it is of the 
same character in each case. As with man and man, so with man 
and the pigeon, — susceptibility is no measure or gauge of the char- 
acter of the impression. 

A large number of drugs — indeed, it may be said, the larger num- 
ber of important drugs — exert in the system antagonistic actions. 
Thus, atropia stimulates the spinal cord, but destroys the conducting 
power of the nerve-trunks. It is evident that as one or other of these 
influences predominates, will there be convulsions or paralysis. Now 
if for any reason one animal be exceedingly sensitive to the spinal 
action of atropia, that animal will in belladonna-poisoning suffer 
from convulsions, while its fellow, which is affected chiefly by the 
nerve-action of the drug, will, under like circumstances, have paral- 
ysis. Here the mere clinician, with his superficial knowledge, seeing 
the paralyzed and the convulsed lying side by side, says, What a 
hopeless muddle! Poor fools, these vivisectors! they will never come 
to any good! In truth, the differences in symptoms in these and 
in many other cases simply depend upon differences in suscep- 
tibility; and the only lesson that the circumstance teaches is the 
importance of discovering the laws which govern these susceptibilities. 

A law which governs the susceptibility to the action of drugs is, 
that the more highly specialized any system is the more readily 
affected is it by a medicine. Thus, the cerebrum of a man is far more 
highly organized than that of any other animal, and consequently 
he is far more sensitive to the action of drugs which affect the cere- 
brum than are the lower forms. Again, in the frog the spinal system 
is especially developed, — probably, in proportion to the cerebrum, 
more so than in any other of the animals commonly experimented 
with: consequently the batrachian is excessively sensitive to reme- 
dies which, like strychnia, affect the spinal cord. In obedience to 
this law, we have resulting the action of opium, — an action which has 
been considered the strongest proof oif the hopelessness of any 
attempt to explain the effects of drugs upon a man by experiments 
upon the lower animals. In man, opium causes deep stupor and 
general relaxation; in the frog, it causes tetanic convulsions. The 
explanation of these seeming inconsistencies is, however, very evident 
when the whole subject is looked at. Opium in all animals has a 
double action, one upon the cerebrum and one upon the spinal centres. 
In the frog, the latter being the more highly organized, the spinal 
action overcomes the cerebral; in man, the cerebrum being the more 
sensitive, stupor replaces the convulsions: yet in man convulsions 
sometimes occur in opium-poisoning, and in the frog the dose can be 
so managed as to cause stupor. 

A second law which seems to hold sway over the action of drugs 
upon different animals is that great differences of function in a system 
affect its relation to drugs: thus, in an herbivorous animal the ali- 
mentary canal is very different from what it is in the carnivora, 



PREFACE TO THE FIRST EDITION xi 

whose digestive organs in turn differ from those of man, — the omni- 
vore. Medicines which act upon the alimentary canal are apt to 
vary in their effects upon different orders of animals. 

Converse to the above law is that which renders systems which 
are little specialized similarly acted upon by drugs in different classes 
of animals. 

Thus, the general structure and the functions of the circulatory 
system are very uniform among vertebrates, as is also the action of 
those drugs which affect chiefly the circulation: thus, aconite, or 
digitalis, or potash, influences in the one way the heart of the frog, 
of the rabbit, and of man. 

There are a very few apparent exceptions to the uniformity of the 
action of drugs upon all animals which seemingly contravene the laws 
that have been mentioned. These exceptions are so few, however, 
that without doubt advancing knowledge will by and by explain 
them all and show what are the laws which for the time being hold in 
abeyance or overcome those already stated. 

An asserted fact which has recently been brought forward as 
revealing the worthlessness of animal experimentation is that some 
monkeys are not susceptible to the action of strychnia, while others 
are. Granting the truth of the asserted fact, it certainly is explain- 
able. It is at least conceivable that a given species of animal may, 
by the gradually acquired habit of feeding upon a substance con- 
taining a narcotic poison, acquire an insusceptibility to the influence 
of that poison which shall as it were belong to its specific type, or, in 
other words, be an acquired specific character. The nervous system 
of the opium-eater becomes accustomed to the stimulant, and it is 
not impossible that a measure of the habit should be transmitted. 
If the Darwinian law of the gradual evolution by the survival of the 
fittest have any force, these curious apparent freaks of medicines in 
regard to their physiological action may be the result of this law, 
especially since it is species which are affected. It is not all monkeys 
that are proof against strychnia, but, as we are distinctly told, only 
one species of monkey; and, so far as I know, it is not all deer that 
are said to thrive when fed upon tobacco, but only the Virginia deer. 
Whether this conception be or be not a mere fancy, this much is to 
my mind very clear, that the few scattered exceptions ought not to 
outweigh the immense mass of evidence upon the other side, and that 
it is inconceivable that drugs, in their relations to animal organisms, 
differ from all other created things in not being subject to law. 

In the early portion of this preface I stated that the work had 
grown out of a need felt by myself: that need was for a book into 
which should be gathered the many scattered facts in regard to the 
physiological action of medicine, — a book in which an attempt should 
be made to sift the true from the false, to reconcile seeming differences, 
to point out what we know and what we do not know, and to give a 
platform from which investigators might start forward without the 
necessity of being, as is so often the case, ignorant of what was already 



xii PREFACE TO THE FIRST EDITION 

achieved, or of spending a great deal of time in a wild hunt through 
the almost boundless, but often scattered and inaccessible, ranges of 
Continental literature. 

The plan of the present work has been to make the physiological 
action of remedies the principal point in discussion. A thoroughly 
scientific treatise would in each article simply show what the drug 
does when put into a healthy man. and afterwards point out to what 
diseases or morbid processes such action is able to afford relief. 
Unfortunately, in the great majority of cases our knowledge is not 
complete enough for this, and the clinical method has to be used to 
supplement the scientific plan. 

I have added to the book a consideration of toxicology, so far as it 
i- of interest to the physician. This has been done for several reasons, 
first . it was necessary to stud}' the action of poisonous drugs upon 
man, in order to make out their physiological action; secondly, 
physicians are constantly required to diagnosticate and to treat cases 
of poisoning; thirdly, it is often of the greatest importance for a 
medical man in a court of law to be able to state what are the symp- 
toms and post-mortem appearances produced by a given poison, 
what diseases they simulate, and how far and in what they differ 
from the phenomena of these diseases. That part of the science of 
toxicology which treats of the recognition of poisons in the cadaver, 
or in food and drink, belongs to the domain of the chemist, and I 
have avoided it altogether. For a similar reason, in the sections on 
materia medica, the chemical relations of mineral substances have 
not been discussed at all. 



ABBREVIATIONS 



A. A. — Archiv fur Augenheilkunde. 

A A. P. — Archiv fur Anatomic und 

Physiologic 
A. C. J. — American Chemical Journal. 
A. D. S. — Archiv fur Dermatologie und 

Syphilis. 
A. de P. — Archives de Physiologie nor- 

male et pathologique. 
A. E. P. P. — Archiv fur experimentelle 
Pathologie und Phar- 
makologie. 
A. Q. M. — Archives generates de Mede- 

cine. 
A. G. P. — Archiv fur die gesammte 
Physiologie des Mens- 
chen und der Thiere. 
A. Hk. — Archiv der Heilkunde. 
A. I. B. — Archives italiennes de Bio- 

logie. 
A. I. M. N. — Archivio italiano per le 

malattie nervose. 
A. I. Past. — Annales de l'Institut Pas- 
teur. 
A. I. P. — Archives internationales de 

Pharmacodynamic. 
A. J. M. S. — American Journal of the 

Medical Sciences. 
A. J. P. — American Journal of Physi- 
ology. 
A. K. C. — Archiv fur klinische Chi- 

rurgie. 
Al. Z. Ps. — Allgemeine Zeitschrift fiir 

Psychiatric 
A. M. Ex. — Archives de Medecine ex- 
perimentelle et d'Ana- 
tomie pathologique. 
Amer. Med. — American Medicine. 
Am. Lan. — American Lancet. 
A. N. — Alienist and Neurologist. 
An. d'H. — Annales d 'Hygiene. 
An. O. — Annals of Ophthalmology. 
Ann. O. — Annales d'Oculistique. 
A. Op. — Archiv fiir Ophthalmologic. 
A. of Op. — Archives of Opthalmology. 
A. Ph. — Archiv fiir Anatomie und 
Physiologie, physiologis- 
ches Abteilung. 
A. Pharm. — Archives de Pharmacody- 
namic 
A. R. — Aerztliche Rundschau. 
A. S. Z. — Aerztliche Sachverstandigen- 

Zeitung. 
Aus. M. Oaz. — Australian Medical Ga- 
zette. 
Aus. M. J. — Australian Medical Journal. 
A. V. K. — Archiv fur Verdauungs- 
Krankheiten. 



A. Z. — Apotheker-Zeitung. 

B. A. M. — Bulletin de 1' Academic de 

M6decine de Paris. 
B. A. R B.— Bulletin de l'Academie 
Royale de Medecine de 
Bel°"c 
B. O. T.— Bulletin general de Therapeu- 
tique medicale et chirurgi- 
calc 
K. Ch. — Beitrage zur klinischen 
Chirurgic 
K. W. — Berliner klinische Wochen- 

schrift. 
M. — Le Bulletin Medicale. 
M. J. — British Medical Journal. 
M. S. C. P.— Bulletin et Memoires 
de la Societe Clin- 
ique de Paris. 
B. M. S. H. — Bulletin Society Medicale 
des Hopitaux des Paris. 
B. M. S. J. — Boston Medical and Surgi- 
cal Journal. 

B. P. A. — Beitrage zur Pathologischen 

Anatomie und zur Allge- 
meinen Pathologie. 

Cb. B. — Centralblatt fiir Bacteriologic 

Cb. C. — Centralblatt fiir Chirurgie. 

Cb. I. M. — Centralblatt fiir Innere Med- 
icin. 

Cb. N. — Centralblatt fiir Nervenheil- 
kunde. 

Cb. P. — Centralblatt fiir Physiologie. 

C. B. S. A. — Correspondenzblatt der 

Schweizerische Aerzte. 
Chi. M. J. — Chicago Medical Journal. 
C. K. M. — Centralblatt fiir klinische 

Medici n. 
CI. M. — Clinica Moderna. 
CI. M. I. — La Clinica Medicale Italienne. 
C. M. J. E. — Chicago Medical Journal 

and Examiner. 
C. M. R. V.— Contributions to Medical 
Research. Vaughn. 
Ann Arbor. 1903. 
W. — Centralblatt fiir medicin- 
ischen Wissenschaften. 
C. R. A. S. — Comptes-rendus de 
l'Academie de Sci- 
ence, Paris. 

C. R. S. B. — Comptes-rendus de la 

Society de Biologie, 
Paris. 

D. A. K. M. — Deutsches Archiv fiir 

klinische Medicin. 
D. C. — Dermatologisches Centralblatt. 
D. J. M. S.— Dublin Journal of the 
Medical Sciences. 



C. M. 



XIV 



ABBREVIATIONS 



D. Kl.— Deutsche Klinik. 

D. M. W. — Deutsche medicinische Wo- 

chenschrift. 
D. Z. Ch.— Deutsche Zeitschrift fur 
Chirurgie. 

D. Z. N. — Deutsche Zeitung fur Nerven- 

heilkunde. 
Ed. M. J. — Edinburgh Medical Jour- 
nal. 

E. M. N.— L'Eel.o Medical du Nord. 
Fort. M. — Fortechritte der Medicin. 

Q. A. M. T. — Giornale della Reale 
Academia di Medi- 
cina di Torino. 
G. H. M. C. — Gazette Hebdomadaire de 
Mc'decine et de Chi- 
rurgie. 
G. I. M. P. — Gazzetta Internazionale de 

Medecina Practica. 
G. K. H. — Monatsberichte iiber die 
gesammtleistungen auf 
dem Gebeite der Krank- 
heiten desHarnundSex- 
ual-Apparates. 
G. M. P. — Gazette Medicale de Paris. 
Gl. M. J. — Glasgow Medical Journal. 
Guy H. R.— Guy's Hospital Re- 
ports. 
Hk. — Die Heilkunde. 
M. S. Jb. — Hoffmann and Schwalbe's 
Jahresberichte iiber die 
Fortschritte der Ana- 
tomie und Physiologie. 
I. B. I. M. — Internationale Beitriige zur 

Inneren Medicin. 
In. Dis. — Inaugural Dissertation. 
J. A. M. A. — Journal of the American 

Medical Association. 
J. A. P. — Journal of Anatomy and Phys- 

. r-x. J ol °gy- 

J. Chem. S. — Journal of the Chemical 

Society of London. 
J. de PA. P. — Journal de l'Anatomie et 

Physiologie. 
J. de Th. — Journal de Therapeutique. 
J. Ex. M. — Journal of Experimental 

Medicine. 
J. M. R. — Journal of Medical Research. 
J. N. M. D. — Journal of Nervous and 

Mental Diseases. 
J. P. — Journal of Physiology. 
J. Pr. — Journal des Praticiens. 
J. P. and B. — Journal of Pathology and 

Bacteriology. 
K. T. W. — Klinisch-Therapeutische 

Wochenschrift. 
L. L — London Lancet. 
Lyon M.— Lyon Medicale. 
L. M. R. — London Medical Recorder. 
L. S. — Lo Sperimentale. 
M. A. — Merck's Archives. 
M. C. C. — Medicinische-Chirurgisches 

Centralblatt. 
M. C. Tr. — Medico-Chirurgical Transac- 
tions. 
Med. R.— Medical Register. 



M. H. H. B. — Marine Hospital Hygienic 

Laboratory Bulletin. 
M. M. W. — Miinchener medicinische 

Wochenschrift. 
M. News. — Medical News. 
M. N. A. S. — Memoirs of the National 

Academy of Science. 
M. P. D. — Monatshefte fur praktische 

Dermatologie. 
M. P. N. — Monatsschrift Psychiatrie 

und Neurologie. 
M. R.— Merck's Report. 
M. S. Rep. — Medical and Surgical Re- 
porter. 
M. T. G. — Medical Times and Gazette. 
M. W. — Medicinische Wochenschrift. 
N. Cb.— Neurologisches Centralblatt. 
N. O. M. J. — New Orleans Medical Jour- 
nal. 
N. Y. M. J.— New York Medical Journal. 
N. Y. M. R.— New York Medical Rec- 
cord. 

N. Y. M. T New York Medical Times. 

0. M. R. — Ohio Medical Recorder. 
O. R. — Ophthalmic Record. 
Pa. M. S. J. — Pacific Medical and Sur- 
gical Journal. 
Path Intern. — Pathologie Interne. 
Ph. Post. — Pharmaceutical Post. 
P. J. and Tr. — Pharmaceutical Journal 

and Transactions. 
P. M. C. P. — Pester medizinisch Chirur- 

gische Presse. 
P. M. J. — Philadelphia Medical Journal. 
P. M. T. — Philadelphia Medical Times. 
P. P. S. L. — Proceedings of the Physio- 
logical Society of Lon- 
don. 
Pract. — Practitioner. 
Press. M B. — La Presse Medicale Bel- 

gique. 
Pr. M. W. — Prager medicinische Wo- 
chenschrift. 
Prog. M. — Le Progres Medicale. 
P. Tr. R. S. L.— Philosophical Trans- 
tions of the Royal 
Society of London. 
Q. J. P. M. — Quarterly Journal of Psy- 
chological Medicine and 
Medical Jurisprudence. 
R. C. — Revue de Chirurgie. 
R. M. S. R.— Revue Medicale de la 

Suisse Romande. 
R. Med. — Revue de Medicene. 
Rif. M. — La Riforma Medica. 
R. T. — Revue de Therapeutique. 
Sb. G. W. — Sitzungsberichte der konig- 
liche Gesellschaft der 
Wissenschaften. 
S. Jb. — Schmidt's Jahrbiicher der in- 
und auslandischen gesamm- 
ten Medicin. 
S. M. — La Semaine Medicale. 
St. L. C. R. — St. Louis Clinical Record. 
St. L. M. S. J.— St. Louis Medical and 
Surgical Journal. 



ABBREVIATIONS 



XV 



S. L. P. C. Y.— Studies from the Labora- 
tory of Physiological 
Chemistry of Yale 
University. 
St. P. M. W. — St. Petersburger med- 
icinische Wochen- 
schrift. 
T. G. — Therapeutic Gazette. 
Ther. Geg. — Die Therapie der Gegen- 

wart. 
Th. M. — Therapeutische Monatshefte. 
T. M. — Therapeutic Monthly. 
Tr. A. O. S. — Transactions of the Amer- 
ican Ophthalmological 
Society. 
Tr. I. C. C. — Transactions of the Inter- 
national Congress of 
Charity, Corrections, 
and Philanthropy. 
Tr. P. C. M. S.— Transactions of the 
Philadelphia County 
Medical Society. 
Tr. R. S. Ed. — Transactions of the 
Society of Edin- 
burgh. 
T. W. — Therapeutische Wochenschrift. 
U. M. M. — University Medical Maga- 
zine. 
U. N. M. T. — Untersuchungen zur Na- 
turlehre des Menschen 
und der Thiere. Mole- 
schott. 
U. P. L. W. — Untersuchungen aus den 
Physiologisches Labo- 
ratorium zu Wiirz- 
burg. 
U. P. M. B. — University of Pennsyl- 
vania Medical Bul- 
letin. 



V. A. P. A. — Virchow's Archivfiir path- 
ologische Anatomie und 
Physiologic 
V. A. S. — Verein der Aerzte in Steier- 

mark. 
V. C M — Verhandl. des Congresses fur 

Innere Medizin. 
V. V. N. K. I. M.— Verhandlungen des 
Vierten Nord- 
ischen Kongresses 
fur Innere Medi- 
zin. 
W. A. W. — Sitzungsberichte der kaiser- 
lichen Akademie der Wis- 
senschaften zu Wien. 
Math. Naturwiss. Kl. 
W. G. H. — Wochenschrift fiir die ge- 

sammte Heilkunde. 
Wb. G. A. W — Wochenblatt der k. k. 
Gesellschaft der 
Aerzte in Wien. 
W. K. R. — Wiener klinische Rundschau. 
W. K. W. — Wiener klinische Wochen- 
schrift. 
W. M. Bl. — Wiener medicinische Blat- 
ter. 
W. M. P. — Wiener medicinische Presse. 
Z. B. — Zeitschrift fiir Biologie. 
Z. C. P. P. — Zeitschrift (Beitrage) zur 
Chemischen Physiologie 
und Pathologie. 
Z. F. H.'I. — Zeitschrift fiir Hygiene und 

Infectionskrankheiten. 
Z. K. M. — Zeitschrift fur klinische Medi- 

cin. 
Z. Mb. — Zeitschrift fur Medicinal- 

beamte. 
Z. P. C. — Zeitschrift fur physiologische 
Chemie. 



TABLE OF CONTENTS 



PRELIMINARY CONSIDERATIONS 

PAGE 

Definitions; Preparations; Indications for the Use of Medicine; General 
Methods of Therapeutics; Modes of Administration; Doses, and the Cir- 
cumstances that Modify Them; the Art of Prescribing and Combining 
Medicines; Incompatibilities; Classification 1 

DIVISION I.— SYSTEMIC REMEDIES 

CLASS I.— GENERAL REMEDIES 
ORDER I.-NERVINES 

Family I. — Calmatives: Musk; Valerian; Ammonium Valerate; Asafetida; 

Sumbul; Hops; Cimicifuga; Cypripedium; Acetic Ether; Lactucarium. . 14 

Family II. — Anesthetics: Nitrous Oxide; Ether; Chloroform; Ethyl Chlo- 
ride; Ethyl Bromide; Pental; Practical Anesthesia; Local Anesthesia; 
Eucaine; Tropacocaine; Orthoform; Stovaine; Practical Local Anesthesia 21 

Family III. — Somnifacients: Opium; Codeine; Peronine; Dionine; Heroine; 
Hydrated Chloral;' Sulphones; Paraldehyde; Ethyl Carbamate; Chlo- 
ralformamide; Amylene Chloral; Hedonal; Isopral; Veronal; Chlo- 
ralose; Chloretone 57 

Family' IV. — Delieifacients: Atropine; Hyoscine; Homatropine Hydro- 
bromide; Indian Cannabis; Coca 94 

Family V. — Excito-Motors: Nux Vomica; Brucine 131 

Family VI. — Depresso-Motors: Physostigma; Hydrobromic Acid and its 
Salts; Bromoform; Bromolein; Bromipin; Monobromated Camphor; 
Nitrites; Erythrol Tetranitrite; Lobelia; Gelsemium; Tobacco; Conium; 
Aspidosperma 145 



ORDER II.— CARDIANTS 

Family I. — Cardiac Stimulants: Ammonium and its Salts; Camphor; Oil 
of Camphor; Camphoric Acid; Oxycamphor; Alcohol; Methyl Alcohol; 
Caffeine; Digitalis; Apocynum; Strophanthus; Suprarenal Glands; Con- 
vallaria; Sparteine; Adonidin 182 

Family II. — Cardiac Depressants: Antimony and its Salts; Veratrum; 
Veratrine; Aconite; Aconitine; Hydrocyanic Acid; Bitter Almonds; 
Benzaldehyde 256 



ORDER III.-NUTRIANTS 

Family I. — Astringents: Tannic Acid; Gallic Acid; Galls; Gambir; Kino; 
Hematoxylon; Rhus Glabra; Krameria; Oak; Hamamelis; Geranium; 
Rose Leaves; Tannalbin; Tannacol; Tannopine; Tannoform; Acetic 
Acid; Agaric; Cotarnine; Aluminum and its Salts; Lead, its Salts and 
Preparations; Bismuth, its Salts and Preparations; Cerium Oxalate; Zinc, 
its Salts and Preparations; Copper, its Salts and Preparations; Silver, its 
Salts and Preparations 283 



xviii TABLE OF CONTENTS 

ORDER III.-NUTRIANTS (Continued) 

PAGE 

1 \mii.v II.— Tonics: Iron, its Salts and Preparations; Manganese, its Salts 
and Preparations; Sulphuric Acid; Hydrochloric Acid; Nitric Acid; 
Nitrohvdrochloric Acid; Phosphoric Acid and its Salts; Hypophos- 
phoroua Acid and it- Balte 323 

1 smii.y III.— Alteratives: Phosphorus; Zinc Phosphide; Arsenic and its 
Preparations; Mercury, its Salts and Preparations; Gold Salts; Iodine, 
its Salts and Preparations; Iodipin; Iodoform; Iodol; Thymol Iodide; 
iphen; Europhen; Soziodol; Iodoformogen ; Cod-Liver Oil; Colchi- 
cum; Ichthvol; Isarol; Sarsaparilla; Guaiac; Mezereum; Taraxacum; 
StilliiiL'ia. Xanthoxylum; Jambul; Thiosinamine; Lecithin; Gelatin; 
Nudem; Thyroid Body; Pituitary Body; Spleen; Antitoxins; Opsonins 338 

Family IV.— Antipkriodics: Cinchona and its Alkaloids; Warburg's Tinc- 
ture; Mcthylthionine Hydrochloride; Eucalyptus 419 

Family V. — Antipyretics: Salicylic Acid and its Salts; Salicylic Esters; 
Salophen; Antipyrine; Acetopyrine; Acetanilide; Acetphenetidin; Phenc- 
ooll Hydrochloride: Salipyrin; Pyramidon 444 

CLASS II.— LOCAL REMEDIES 

Family I. — Stomachics: Quassia; Gentian; Calumba; Chirata; Berberis; Wild 
Cherry; Orexin; Volatile Oils; Cinnamon; Cloves; Nutmeg; Pimenta; Car- 
damom; Ginger; Pepper; Capsicum; Chamomile; Serpentaria.- _ 475 

Family II. — Emetics: Ipecacuanha; Apomorphine; Mustard; Zinc Sulphate 485 

Family III. — Cathartics: Enemata, Laxative Foods; Rhubarb; Aloes; Senna; 
Khamnus; Phenolphthalein; Saline Cathartics; Mercurials; Jalap; Colo- 
cynth; Bcammony; Podophyllum; Elaterium; Gamboge; Castor Oil; 
( iroton Oil '. - 497 

Family IV. — Diuretics: Water; Squill; Scoparius; Mercury; Xanthin Com- 
pounds; Theobromine; Agurin; Paraxanthin; Theophyllin; Potassium 
and its Salts: Lithium and its Salts; Piperazin; Sugar; Strontium and its 
Salts: Buchu; Dva Ursi; Pareira; Chimaphila; Triticum; Turpentine; 
Copaiba: Cubeb; Matico; Juniper; Oil of Erigeron; Oil of Santal; Kava; 
Yohimbine; Hexamethylenamine 525 

Family V. — Diaphoretics: Turkish Baths and Russian Baths; Pilocarpus... 559 

Faiuli VI. — Expectorants: Atomization; Lobelia; Antimony and Potas- 
sium Tartrate; Ipecacuanha; Apomorphine Hydrochloride; Potassium 
Citrate; Saponin; Senega; Quillaja; Terpin Hydrate; Terebene; Tar; 
Gnndelia; Balsam of Peru; Balsam of Tolu; Ammoniac; Marrubium; 
Sanguinaria; Sulphuretted Hydrogen 570 

Family VII. — Emmknagogues: Savin; Rue; Tanacetum; Oil of Hedeoma; 

Apiol; Potassium Permanganate; Viburnum 579 

Family VIII. — Oxytocics: Ergot; Hydrastis; Hydrastinine; Cotton-Root.. 582 

Family IX. — Irritants and Counter-Irritants: Soap; Soft Soap; Chry- 
sarobin; Cantharides; Mustard; Capsicum; Arnica; Burgundy Pitch; 
Carbon Disulphide 600 

Familt X. — Escharotics: Potassium Hydroxide; Vienna Paste; Arsenic 
Trioxide; Zinc Chloride; Mercury Bichloride; Mercuric Nitrate; Nitric 
Acid; Chromium Trioxide; Trichloracetic Acid; Bromine; Pyrogallol; 
Lactic Acid _ 611 

Family XL — Demulcents: Gum Arabic; Tragacanth; Slippery Elm; Irish 
Moss; Licorice Root; Flaxseed; Starch; Sassafras; Althaea; Iceland 
Moss; Barley „ ... 617 

Family XII. — Emollients: Comparison of the Various Ointment Bases; Olive 
Oil; Oil of Theobroma; Wool-Fat; Petrolatum; Glycerol; Benzosulphi- 
nide; Kaolin; Poultices; Collodion 621 



TABLE OF CONTENTS xix 

DIVISION II. — EXTRANEOUS REMEDIES 

PAGE 

Family I. — Antacids: Sodium and its Salts; Magnesia; Calcium, its Salts and 

Preparations 631 

Family II. — Anthelmintics. — Santonica; Spigelia; Oil of Chenopodium; As- 
pidium; Pepo; Kousso; Pomegranate Rind; Thymol; Oil of Turpentine; 
Kamala; Azedarach; Picric Acid 639 

Family III. — Digestants: Pepsin; Pancreatin; Malt; Papain 649 

Family IV. — Absorbents: Animal Charcoal, Wood Charcoal. 652 

Family V. — Disinfectants: Cold and Heat; Mercury; Silver; Chlorine; 
Fluorine; Potassium Permanganate; Hydrogen Dioxide; Acetozone; 
Phenol; Salol; Phenol-Sulphonic Acid; Creosote; Guaiacol; Cresol; 
Naphthalene; Betanaphthol; Betol; Menthol; Thymol; Resorcinol; 
Oxalic Ocid; Formaldehyde; Volatile Oils; Benzoin; Benzoic Ac*d; 
Cinnamic Acid; Sulphur and its Oxides; Boric Acid; Practical Disinfection 653 

APPENDIX 

Apothecaries' Weight and Measure; Metric Weights and Measures; Relation of 
Apothecaries' Weights and Measures to each other; Relation of Apothe- 
caries' Measure to Cubic Measure; Relation of Apothecaries' Weights 
to Metric Weights, and of Metric to Apothecaries' Weights; Table of the 
Alcoholic Strength of Wines, of Malt Liquors, and of Distilled Liquors 706 

Index of Diseases _ 711 

General Index _ _. _ ._ „_ _ _ _ — 759 



THERAPEUTICS: 

ITS PRINCIPLES AND PRACTICE 



DRUGS: 

A SKETCH OF THEIR NATURAL HISTORY AND PHARMACEU- 
TICAL PREPARATIONS, WITH AN EXHAUSTIVE STUDY 
OF THEIR PHYSIOLOGICAL, THERAPEUTICAL, 
AND TOXICOLOGICAL ACTIONS. 



PRELIMINARY CONSIDERATIONS. 

Therapeutics is the science of the treatment of disease, includ- 
ing the use not only of chemical agencies (drugs), but also of various 
physical agencies, and the regulation of the mode of living. The 
science which treats of drugs is called Pharmacology. Pharma- 
cology includes Materia Medica, the study of the physical proper- 
ties of substances used as medicines; Pharmacy, the science of 
preparing and combining drugs; and Pharmacodynamics, or the 
study of the effect of drugs upon the healthy animal organism 
(physiological action). 

In every civilized country there is some recognized official list of 
drugs and their preparations, known as the Pharmacopoeia. Until 
recently the United States Pharmacopoeia was the standard by 
courtesy, rather than legal enactment, but adherence to its rules is 
now required by the Federal government as well as by most of the 
States. 

Drugs are derived from the animal, mineral, and vegetable king- 
doms; the greater number of them, however, are of vegetable origin. 
Vegetable drugs as a rule contain some definite chemical substance 
to which they owe their remedial properties, and which is, therefore, 
known as the active principle. 

A number of these active principles belong to the class of sub- 
stances known as alkaloids. An alkaloid may be defined as a sub- 
stance of vegetable origin which is capable of playing the part of an 

l 



o PRELIMINARY CONSIDERATIONS 

alkali in so far that it forms salts with the acids. As a rule alkaloids 
themselves are not freely soluble in water, but the salts which they 
form are very frequently so; therefore, with one or two exceptions 
the alkaloids are usually employed in the form of some salt. Exam- 
ples: Morphine, Strychnine, etc. 

A glucoside is a proximate principle of vegetable origin which can 
be broken up by mineral acids into a sugar and another radical. 
Examples: Strophanthin, Salicin, etc. 

Resins are complex bodies uncrystallizable and usually insoluble 
in water, but freely soluble in alcohol, ether and chloroform. Many 
of them have acid properties. Allied to the resins are the so-called 
uh on sins, which are really mixtures of a resin with a volatile oil. 

The volatile oils represent the active principles especially of many 
aromatic plants. They have a strong odor, are very slightly soluble 
in water, but usually soluble in alcohol and ether. They differ from 
the fixed oils in their greater aroma, but especially in the fact thai 
when evaporated they leave behind no residue, and that they are not 
saponified by the alkalies. Examples: Oil of Wintergreen, Oil of 
Peppermint, etc. 

Many principles of indefinite character have been grouped together 
under the head of neutral principles. These are usually of bitter 
taste but differ from alkaloids in that they do not form salts with the 
acids. Various organic acids may also be the active principles of drugs. 

Remedial agents of organic origin usually require more or less 
pharmaceutical manipulation before they are suited for medical uses. 
The preparations which are made from drugs are commonly known 
as galenicals, from Galen, the famous Roman physician who lived 
in the second century. 

The most important of the official preparations are: 

Decoctions (Decocta) are made by boiling crude drugs for a 
greater or less time in water. It is evident that this method of pre- 
paring is ineligible when the active principle is volatile or is easily 
decomposed by heat, or when the drug contains much starch, whose 
extraction would make the preparation very thick and predispose it 
to rapid decomposition. The method is especially adapted to hard, 
woody substances, and to those containing much albumin, which is 
coagulated by the boiling water and left in the original drug. 

Infusions (Infusa) are made with water,, either cold or hot, 
without boiling. They are prepared by maceration or by displacement. 

Solutions (Liquores) are preparations in which an active, non- 
volatile principle is dissolved in water. 

Waters (Aqua?) are solutions of volatile principles in water. 

Mixtures (Misturce) are preparations in which one or more 
medicinal substances are held in suspension in water. Of such nature 
are emulsions (Emulsa), in which some oily material is suspended by 
a gummy or an albuminous body. 

Syrups (Syrupi) are sugary liquids, the menstruum or basis of 
which is water, with, in some cases, vinegar or alcohol. 



PRELIMINARY CONSIDERATIONS 3 

FLUIDEXTRACTS (Flnidc.rtracta) are solutions of vegetable drugs in 
alcohol, SO made thai one minim represents one grain of the drug. 

Tinctures (Tincturoe) are alcoholic solutions prepared by macera- 
tion or displacement from the crude drug, or by dissolving non- 
volatile principles. They are of varying strengths from 5 to 50 per 
cent.: the poisonous tinctures are nearly all 10 per cent, preparations. 

Spirits (Spiritus) are alcoholic solutions of volatile principles, 
made by direct solution or by distillation from the crude drugs. 

Winks (Vina) are preparations whose menstruum is wine. 

Vinegars (Aceta) are preparations in which vinegar or dilute 
acetic acid is used as the menstruum. 

GlyCERITES (Glycerita) are preparations in which glycerin is the 
solvent. 

Oleatks (Olcata) are solutions of definite principles in oleic acid. 

Solid Extracts (Extracta) are of two kinds; one being prepared 
by the evaporation of the fresh juice, the other being made in various 
ways from the crude drug. They are of a consistency suitable for 
making pills. 

Confections (Confection.es) are medicinal substances beaten up 
with sugar into a pasty mass. 

Troches (Trochisci), or lozenges, are gummy pellets or disks, so 
made as to dissolve slowly in the mouth. 

Suppositories (Suppositoria) are conical bodies, prepared for 
introduction into the rectum, where they melt with the heat of the 
body. Their basis is generally cacao butter. 

Ointments and Cerates (Unguenta and Cerata) are solid, fatty 
preparations for external use. The cerates containing wax (cera) are 
the firmer of the two. 

Plasters (Emplastra) are solid substances spread by the aid of 
heat upon muslin, skin, or other similar material, and of such nature 
as to be adhesive at the temperature of the body. 

Liniments (Linimenta) are liquid preparations, for external use. 

The names Pills (Pihdce) and Powders (Pulveres) sufficiently 
indicate the character of the preparations. 

The effects of medicine are commonly divided into the direct and 
indirect. An example will probably show the difference between 
these in the briefest and most forcible manner. Thus, the direct 
effect of a diuretic is increased urination; the indirect effect may 
be removal of serous effusion in some part of the body which is brought 
about not by the medicine itself, but by the changes it induces; the 
increased excretion causing a diminution of the amount of the fluid 
in the blood-vessels, which in turn leads to absorption. The term 
local action indicates the effects of drugs upon that part of the body 
with which they first come in contact, as the stomach; by general 
action is understood their effects on distant parts of the body to which 
they are carried by the blood after being absorbed. 

The term or expression "indication" for a given remedy, being 
in constant use, ought to be clearly understood; by it is meant the 



4 PRELIMINARY CONSIDERATIONS 

pointings of nature, or, in other words, the evident needs of the 
system. Thus, hard feces collected in the colon are an indication 
for a purgative of such character as will produce watery secretions 
to soften them. Relaxation in a part indicates a remedy that will 
awaken into new life the natural contractility of the part — i.e., an 
astringent. 

Methods of Administering Drugs. — To exercise a general action 
drugs must be absorbed into the blood, and thus find access to the 
part upon which they act. It is necessary, therefore, for them to 
be so placed that they can be taken into the blood-vessels. 

There are six paths of entrance for medicines into the circula- 
tion, — the stomach, the cellular tissue, the rectum, the skin, the 
lungs and by intravenous injection. By far the most frequently 
employed of these is the stomach. It is evident that, in order to pass 
rapidly and readily into the absorbents, medicines must be in solution. 
When administered by the stomach, however, it is equally plain that 
solubility in an ordinary menstruum, such as water, is not a sine 
qua non, since the varying acidities, alkalinities, and organic contents 
of the alimentary juices give to them a solvent power far above that 
of less complex and varying fluids. Thus, a medicine insoluble in 
water may be dissolved by the acids of the gastric juice, while another 
drug may owe its activity to its solution by the alkalies or by the 
fatty matters of the intestinal fluids. 

The dissolving power of the rectal fluids is very slight: hence, in 
order to act efficiently, medicines when given by the rectum must 
be in solution or be readily soluble. Absorption, moreover, does not 
occur so rapidly from the rectum as from the upper bowel, and a 
longer time is therefore needed to impress the system in this way. 

Medicines which are thrown into the subcutaneous tissue are said 
to be administered hypodermically. The syringe employed is pro- 
vided with a sharp needle, which must be kept scrupulously clean 
and free from rust. The medicine must be in perfect solution and 
not too irritating. The advantages of this method of exhibition are 
promptness and certainty of action. If twenty minutes be required 
for the absorption of a certain medicine from the stomach, forty 
minutes will be usually necessary when it is exhibited by the rectum 
and five minutes when it is thrown into the subcutaneous tissue. 
The objections to the hypodermic method are, first, the danger of 
producing local inflammation and abscesses; second, the possibility 
of throwing the whole mass directly into a vein and having it swept 
in concentrated form into the heart or nerve-centres. We have seen 
the injection of one-sixth of a grain of morphine followed inside of a 
minute by complete unconsciousness, collapse, arrest of respiration, 
dropping of the jaw, and apparent death. The danger of such a 
mischance can be greatly lessened by withdrawing the point of the 
needle an eighth of an inch, after it has been plunged into the tissue. 
The local irritation occasioned by hypodermic injections has not only 
very frequently produced abscesses, but in not a few cases has caused 



PRELIMINARY CONSIDERATIONS 5 

fatal tetanus. Excessive irritation can be largely prevented by certain 
precautions, but there are many medicinal substances whose hypo- 
dermic employment might be advantageous were they not too irritant 
for such use. In all cases solution must be complete, and if the medic- 
inal substance be of such nature that it is liable to be precipitated by 
alkalies, an excess of acid should be present in the water to prevent 
precipitation by the juices of the cellular tissue. An irritant which 
is rapidly taken up from the part may produce at first smarting and 
pain without creating any permanent irritation, but a small solid 
particle lying in the cellular tissue is almost sure to cause inflammation 
anil abscess. All hypodermic injections should, therefore, be filtered 
before being used. It is of the utmost importance, even when a non- 
irritating substance is employed, that the injection should be abso- 
lutely aseptic. No solution which has undergone any decomposition 
or contains any growth should be used. Ordinarily the solution 
should be freshly made with boiled water. When hypodermic solu- 
tions are intended to be kept, they should contain three per cent, of 
phenol with a drop or two of glycerin to every fifteen minims, which 
is the maximum amount that should be injected at one time. A 
considerable proportion of glycerin will throw out of solution most 
of the alkaloids, but when solution of the medicinal substance is 
distinctly favored by glycerin, as is the case with extracts, three or 
four minims of the glycerin should be added to the hypodermic 
solution. If the injection be thrown directly under the skin, it may, 
by raising and tearing the skin from its attachment, so interfere with 
the supply of blood as to cause local irritation. Irritant substances 
should, therefore, always be thrown deeply into the tissues, where 
they may diffuse themselves. 

The skin can be used successfully as a mode of introducing drugs 
only if the medicament is volatilizable or else is in fatty solution, as 
in certain ointments. Formerly, medicines were sometimes exhibited 
by placing them on blistered surfaces, beneath the raised cuticle; 
at present this endermic method is very rarely employed. 

In order for a medicine to be absorbed through the lungs it must 
be vaporizable at the body temperature, and not too irritant to be 
inhaled. 

The intravenous injection, on account of the dangers and the 
elaborate technique required, is rarely resorted to except in extreme 
cases. 

For local purposes medicines are applied to various parts, — to the 
skin, ear, nares, fauces, stomach, larynx, lungs, rectum, vagina, 
urethra, etc. For the last three, liquid preparations known as injec- 
tions, or solid ones known as suppositories, or, in case of the urethra, 
as bougies, or sometimes as urethral suppositories, are employed. 

For the purpose of making local applications to the respiratory 
organs, atomization is very commonly practised. Many forms of 
apparatus are in use, but the principle in all of them is the same. 
A rapid current of air, or of steam, is forcibly ejected from a hori- 



* 



6 PRELIMINARY CONSIDERATIONS 

zontal pipe, through a capillary orifice, directly across a similar open- 
ing in a vertical tube. The rush of the vapor over this second orifice 
forms a vacuum: the fluid into which the base of the vertical tube 
is Bet, rushing up to fill (his. is Bucked or drawn out through the orifice, 
and as it emerges is broken into a fine spray, and is carried along by 
the current of air or steam into a mouthpiece, at which sits the patient. 
It cannot be gainsaid that in this way we are able to carry medicinal 
substances not merely into the larynx, but into the lungs themselves. 
Volatile medicines vaporized by heat are also sometimes employed 
in the treatment of lung affections. 

There are various classes of agencies which so modify the action 
of drugs as to necessitate their consideration. Such are disease, 
climate, habit, temperament, idiosyncrasies, sex, age, time of admin- 
istration, and emotions. 

Disease often fortifies the system against the action of remedies, 
so that the dose has to be greatly increased to obtain perceptible 
effects. Thus, pain or delirium tremens will interfere greatly with 
the production of narcotism by opium. Disease may altogether 
prevent the action of a remedy. In all these cases two rules should 
never be lost sight of: first, never give the medicine in such doses as 
would in health cause death; second, always be sure, before giving 
large amounts, that the remedy will not make matters worse (as a 
drastic purgative in intussusception). 

Climate, by producing physical habits or tendencies in the patient, 
often greatly influences the proper selection and dose of remedies. 
It is only necessary to allude to the great consumption of quinine in 
malarial regions as an example. 

Habit — including mode of life — seems to alter, as it were, the very 
constitution of man. Not only does it give type to disease, by pro- 
ducing habitual plethora, or its opposite, but it also fortifies against 
the action of single remedies, or whole classes of them. Thus, in the 
opium-eater, a dose sufficiently large to kill an ordinary man serves 
only to gratify the cravings of appetite. Again, a man accustomed 
to one narcotic, as alcohol 01 opium, loses, to a greater or less degree, 
his susceptibility to all narcotic influence; and the patient whose 
bowels require daily to be moved by a cathartic finds that he reacts 
more and more slowly to medicines of that class. Again, a nervous 
system blunted by exposure and toil in the open air is far less sus- 
ceptible to the action of remedies, and requires larger doses to influence 
it, than does the delicate organization of a woman weakened by 
indolence and luxury. 

Temperaments are peculiarities of organization characterizing 
classes of individuals; idiosyncrasies, peculiarities belonging to single 
individuals. This is scarcely the place to discuss the subject of tem- 
peraments, but it is allowable to state that while the phlegmatic 
person is no more easily moved by medicinal than by other agencies, 
the nervous individual answers as quickly to the one as to the other. 
Idiosyncrasies seem at present to be beyond law. They are often 



PRELIMINARY CONSIDERATIONS 7 

very remarkable, and a knowledge of them is most important for 
the practitioner. Thus, a relative of the authors' is thrown into the 
most alarming fainting-fits by eating even so much butter as would 
be ordinarily used as a dressing for vegetables at dinner. Some 
persons are poisoned by the slightest touch of turpentine, others are 
frightfully salivated by a mere particle of a mercurial. These idiosyn- 
crasies are numerous, cannot be foreseen, and are often very impor- 
tant: hence the necessity, in prescribing for an unfamiliar patient, 
of always asking as to his or her peculiarities. 

Sex modifies all diseases connected with the organs or the process 
of generation, but it also does more. Woman is more impressible, 
less robust, with less power of resisting external agencies, than is 
man; consequently, the dose for her should, as a rule, be less than 
that for him. It is needless to remark here at length on the necessity 
for abstinence from strongly perturbing remedies during pregnancy 
or at menstrual periods. 

Age, of course, modifies materially the dose. The rule of Young, 
the one which is the most practical and generally useful, is to add 
twelve to the age and divide the age by the result. Thus, a child 
one year old would require one-thirteenth, one three years old three- 
fifteenths, of the amount necessary for an adult.* 

Purgatives should usually be given to children in larger, narcotics 
in much smaller, doses than are called for by Young's rule. 

Time of Administration. — Absorption takes place most rapidly in 
an empty stomach, and consequently, when rapidity of action is 
desired, the medicine should be given under such circumstances. 
Thus, a purgative acts soonest when given before breakfast. Sub- 
stances which are irritating to the stomach should always be admin- 
istered, not only properly diluted, but also when the viscus is filled 
by a mass of food, which may serve still further to lessen their concen- 
tration. Hence such remedies as iodine and arsenic are preferably 
exhibited after meals. On the other hand, whenever a remedy is 
especially intended to act on the mucous membrane of the stomach, 
it should be given when the viscus is empty. Again, some drugs, 
such as iron, are best dissolved by the acid gastric juice, and it is a 
matter of some importance to place them in the stomach after eating, 
when the process of digestion is most vigorous. 

Mental Emotion. — Space is wanting to discuss at any length the 
influence of the imagination upon the action of remedies, and the 
reader is referred to the delightful book of Tuke for illustrations. 
Suffice it to state that a positive announcement that a remedy will 
have a certain effect has often a most remarkable influence in pro- 

* Clarke's rule (.Boston Med. and Surg. Journ., 1872) is based upon relative weight. 

"Assuming the average weight of an adult to be one hundred and fifty pounds, for whom 
an appropriate dose is i, or one drachm, the dose of most medicines must be increased or dimin- 
ishecf in the proportion of the weight of the patient to that number of pounds. This proportion 
is represented by a fraction whose numerator is the patient's weight and whose denominator is 
150. If a child at birth weighs six pounds, the appropriate dose for it would be ifo, or 2 "j; if 
it weighs ten pounds, J& or &. A child two years old, weighing twenty pounds, would require 
t^o, or about i of an adult dose; or, more precisely, 7^. A person whose weight is two hundred 
pounds should have t§8. or 1 J of an average adult dose." 



8 PRELIMINARY CONSIDERATIONS 

during that effect, especially on persons of nervous organization and 
of not too great culture to have faith. We have given a hypodermic 
injection of one-fourth grain of morphine to a man. inducing a degree 
of hypnotism, and the next day, doubling the size of the injection but 
withdrawing all morphine, have caused a much more intense effect. 

On the Art of Prescribing Medicines. — In the practical use 
of remedies, very much depends upon the methods of their combina- 
tion, and, so far as concerns the reputation of the physician, no little 
importance is to be attached to the mere prescription-wTiting. The 
recipes of the master are very widely seen, and he who is incorrect 
in the grammar or spelling of his English or Latin, or departs without 
reason from the traditional forms, lays himself open to ridicule, than 
which nothing is more damaging. A crooked, bad chirography is 
the traditional mark of literary fame; but absolute plainness should 
be a sine qua non in the writer of prescriptions. This should also 
apply to abbreviations: these should be of such a character as not 
only to be readily made out, but also to be so evident as to afford 
no shelter to the apothecary whose carelessness may lead to serious 
error. In the case of alkaloids and other powerful remedies, the 
chief name at least should be written in full. In writing the pre- 
scription, all the ingredients should first be put down, then the number 
of doses should be decided upon, and the individual amounts of 
each substance marked seriatim. It is a very good custom always 
to place first upon the list the strongest of the drugs employed. 

The art of combining remedies is not a difficult one; but in practice 
certain principles should not be lost sight of. Chief of these are, to 
prescribe as few remedies as possible, and to use no powerful drug 
without a very distinct idea of what it is intended to do. Whenever 
it is desired to give a powerful remedy in increasing doses until its 
physiological effect is produced, it should always be given by itself. 
Thus, it may be necessary to give arsenic so as to impress the system, 
at the same time that iron is indicated; but the two remedies should 
be given separately, so that the dose of either can be increased or 
diminished independently of the other. 

The principles of combination, formulated below, were long ago 
enunciated by Paris, but are to-day as imperative as ever. Medicines 
are combined, — 

First. — To augment, correct, or modify the action of a medicine. 
Thus, purgatives act much more kindly when a number of them are 
united together. The chief reason of this probably is, that as different 
remedies affect different portions of the gut, the whole intestine is 
best reached by a union of the diverse substances. It may take an 
intense irritation of the mucous membrane to purge as actively as 
does a mild irritation of both the mucous membrane and the 
muscular coat. 

There are powerful medicines which act similarly upon some parts 
of the organism, but dissimilarly upon other parts. By combining 
such remedies powerful effects can be obtained at the points where 



PRELIMINARY CONSIDERATIONS i) 

the two lines of action cross each other, without influencing to a 
great extent other portions of the system. Thus, chloral produces 
sleep by its action upon the brain, and also has a distinct influence 
upon the heart, but none upon the intestinal tract. Morphine acts 
upon the brain, and does not influence the heart, but has a powerful 
effect upon the intestinal tract. By combining chloral and mor- 
phine we get an overwhelming conjoined influence upon the brain 
in producing sleep with the least possible disturbance of the heart 
and of the intestinal tract. 

Secondly. — To obtain the joint action of two or more diverse 
remedies. Thus, in a cough mixture, morphine may be included to 
quiet the cough, while ipecacuanha and squill (in accordance with 
the first principle) are added to affect the mucous membrane. The 
application of this principle requires caution, or the practitioner will 
be led into that chief abomination, polypharmacy. It is worse than 
futile to attempt to prescribe for every symptom. It is the underlying 
cause of the disorder or the understratum of bodily condition which 
must be sought out and prescribed for simply. 

Thirdly. — To obtain a special combination which is really a new 
remedy, or which experience has shown acts almost as a new remedy. 
Thus, when to potassium iodide in solution corrosive sublimate is 
added, a new chemical compound is formed, which experience has 
shown to be of great value in syphilitic diseases. In the famous 
Dover's powder (Pulvis Ipecacuanha? et Opii) no chemical change 
occurs, but the ordinary action of opium upon the skin is so 
enhanced that the combination may be looked upon almost as a 
new remedy. 

Fourthly. — To afford a suitable form. Thus, acacia is added to 
make an emulsion, or confection of rose to make a pill. In the choice 
of excipients, care should be exercised to select a substance free from 
medical properties, having no chemical incompatibility with the 
medicinal agent, and of suitable physical character. When writing 
a prescription, the utmost care should be taken to use such excipients 
that the combination shall not only be attractive to the eye, but 
also as slightly repulsive to the palate as may be. Whenever possible, 
the pill form should be employed with bitter or disagreeable medicines. 
In regard to mixtures, flavoring oils should be freely used, and the 
power of glycerin to conceal the disagreeable taste of many substances 
should be remembered. Whenever practicable, nauseous medicines 
should be given in capsules. These occur in two forms. Hard capsules 
are prepared to be filled extemporaneously. They can be made 
large enough to hold ten grains, although this size cannot be easily 
swallowed by every person without a little training. The soft, flexible 
capsules are filled by the manufacturing chemists. They can be 
readily swallowed by most persons up to the size of one drachm. 
Not only may solid preparations be given in capsules, but also essential 
oils, volatile liquids, fixed oils, and fluidextracts; indeed, almost any 
liquid the dose of which is not too large. 



10 PRELIMINARY CONSIDERATIONS 

Incompatibilities. — In combining remedies, the subject of incom- 
patibilities must never lie lost sight of. The kinds of incompatibilities 
are three in number, — physiological, pharmaceutical and chemical. 
The first of these it would require large space to disruss fully, and 
any one familiar with the text of the book, if possessed of the slight- 
est reasoning powers, can readily make all necessary deductions. 

Pharmaceutical incompatibilities are mostly dependent on the 
different solvent powers of water and alcohol. Speaking generally 
vegetable substances are more readily soluble in alcohol than in water. 
For this reason the alcoholic tinctures contain various resinous mat- 
ters which are insoluble in water, and the mixture of such a tincture 
with an aqueous menstruum frequently causes a precipitation which 
makes an unsightly mixture or may even interfere with its efficacy. 
In this connection attention may be called to the precipitation of 
acacia by alcohol; therefore emulsions should always be made with 
a watery menstruum. 

The inorganic drugs are more generally soluble in water than in 
alcohol. For accurate data concerning the solubility of official chemi- 
cals the reader is referred to the United States Pharmacopoeia; but 
the most important relations are covered by the following rules: 
All of the official salts of potassium, except the bitartrate, are soluble 
in water; all the official salts of sodium and of ammonium are soluble 
in water; all the salts of mercury except the bichloride are insoluble; 
the salts of the other bases vary in their solubility too much to allow 
a brief summarization. All of the official salts of the following acids 
are soluble: Hydrobromic, hydrochloric, hydriodic, acetic, citric, 
benzoic and salicylic. Basic alkaloids are, as a rule, almost insoluble 
in water, their salts are usually easily dissolved by water but less 
readily by alcohol. 

In many works on materia medica long lists of chemical incompati- 
bilities are given in the accounts of individual drugs. These lists have 
seemed to us useless, as we have never met with a student who could 
commit and retain them. Moreover, they contain so much matter 
of no practical use that the valuable portion is hidden from sight. 
A certain amount of chemical knowledge is essential to the student, 
and is not to be taught in a book like the present. He who would 
ignorantly combine sulphuric acid and the carbonates, needs to 
restudy his chemical text-book. All that we shall do here is to point 
out certain principles and a few reactions. The following rules may 
serve as a guide. 

When two salts can, by any change of their radicals, form an 
insoluble compound such change will take place and precipitation 
occur; soluble salts which are not capable of forming an insoluble 
compound never precipitate and rarely undergo decomposition when 
they meet in solution. 

Mineral acids decompose salts of the vegetable (carbonic, acetic, 
etc.) acids and form ethers with alcohol. They also decompose the 
glucosides. 



PRELIMINARY CONSIDERATIONS 11 

Salts of the alkaloids are precipitated from aqueous solution by 
the alkalies including carbonates and borates, by the iodides,* cor- 
rosive sublimate and tannic acid. Antipyrine is incompatible with 
all the alkaloidal precipitants and also with spirit of nitrous ether, 
with tincture of ferric chloride, and with calomel; it is liquefied by 
hydrated chloral, by salol and by various other members of the aro- 
matic series. 

Tannic acid is incompatible with the alkaloids, glucosides, gelatin, 
albuminous bodies and most of the soluble metallic salts. 

Silver nitrate and corrosive sublimate are each incompatible with 
almost every drug in the Pharmacopoeia, as are also the acetate 
and subacetate of lead. 

Preparations containing iron are incompatible with salicylic acid 
and its salts. With nearly all the vegetable galenicals they form 
a black precipitate due to the fact that practically all vegetable 
products contain tannic acid — from this latter group may be 
excepted quassia and calumba. The salts of iron are also precipi- 
tated by alkalies. 

The following preparations contain free acid and should not be 
prescribed with alkaline carbonates: Fluidextracts of conium, ergot, 
lobelia, nux vomica, sanguinaria and squill; the syrups of squill, 
ipecac, hypo phosphites and orange; the solutions of ferric chloride, 
of hydrogen dioxide and of iron and ammonium acetate, and fre- 
quently the spirit of nitrous ether. The following are alkaline in 
reaction and should not be combined with acids: Aromatic fluid- 
extract of cascara sagrada, fluidextracts of licorice, of senega, and 
of taraxacum, the solution of potassium arsenite and the syrup of 
rhubarb. 

Classification. — While it is impossible to devise any arrange- 
ment of drugs which is perfectly satisfactory in all respects, the fol- 
lowing schema, which follows the principle of all systematic arrange- 
ments in biological science, is, we believe, of great service to the 
student in enabling him to associate together drugs having similar 
effects. 

Division I. — Systemic Remedies, substances which act on the 
solid or fluid tissues of the body. 

Division II. — Extraneous Remedies, substances which are em- 
ployed to act on secretions, excretions, or other liquid or solid bodies 
which are not human tissues. 

SYSTEMIC REMEDIES. 

Class I. — General Remedies, drugs which affect the tissues of 
the body generally or such organized systems as reach all portions of 
the body. 

Order I. — Nervines, drugs which affect the nervous system. 

* Death has resulted from a prescription containing strychnine and potassium iodide, all 
the alkaloid being taken at the last dose. 



12 l'KKLIMINARY CONSIDERATIONS 

Order II. — Cardiants, drugs which affect the circulation. 
Order III. — Nutriants, drugs which affect the nutritive processes 
of the body. 

NERVINES. 

A. Medicines which act on the cerebrum. 

It. Medicines which act on the lower or neuro-muscular apparatus. 

A. 

Family I.— Calmatives, feeble cerebral .stimulants which are em- 
ployed for the relief of minor spasms and other nervous symptoms, 
the result of insufficient nerve-power. 

Family II. — Anesthetics, drugs which are used for the production of 
anesthesia. 

Family III. — Somnifacients, drugs which when in sufficient doses 
produce deep sleep without delirium. 

Family IV. — Delirifacienls, drugs which when in sufficient doses 
produce delirium, followed by stupor. 

B. 

Family V. — Excito-motors, drugs which produce violent tetanic 
spasms. 

Family VI. — Depresso-motors, drugs which cause paralysis. 

CARDIANTS. 

Family I. — Cardiac Stimulants, drugs which increase the activity 
of the heart. 

Family II. — Cardiac Depressants, drugs which lessen the heart 
action. 

NUTRIANTS. 

Family I. — Astringents, drugs which call into exercise the vital 
function of contractility. 

Family II. — Tonics, drugs which so influence nutrition as to 
increase the reconstruction or upbuilding of the tissue or tissues 
concerned. 

Family III. — Alteratives, drugs which so modify nutrition as to 
overcome certain chronic pathological processes. 

Family IV. — Antiperiodics, drugs which are used to overcome 
the effects of malarial poisoning. 

Family A'. — Antipyretics, drugs which so modify nutrition as to 
overcome febrile movements. 

Class II. — Local Remedies, drugs which affect one organ or 
apparatus more or less isolated from the remainder of the body. 



PRELIMINARY CONSIDERATIONS 



13 



Family I. 


— Stomachics* 


II. 


Emetics. 


III. 


— Cathartics. 


IV. 


— Diuretics. 


V. 


— Diaphoretics. 


VI. 


— Expectorants. 


VII. 


— Emmenagogues 


Family 1. 


EXTRAN 

— Antacids. 


II. 


— Anthelmintic 


III. 


— Digestants. 



Family VIII. — Oxytocics. 
IX. — Irritants. 
X . — Eschar otics. 
XI. — Demulcents. 
XII. — Emollients. 
XIII. — Protectives. 



5 REMEDIES 

Family 



IV. — .4 bsorbents. 
V. — Disinfectants. 



* The definitions are not given in these families, as they are old and well known and their 
names show the reader to what organs each applies. It should be stated, however, that the family 
stomachics contains drugs which are used simply as stimulants to the gastro-intestinal tract, includ- 
ing therefore, Simple Bitters, so called, and Aromatics. 



DIVISION I— SYSTEMIC REMEDIES. 
CLASS I— GENERAL REMEDIES. 
ORDER I.— NERVINES. 



FAMILY I.— CALMATIVES.* 

In certain conditions of the nervous system— conditions associated 
with weakness rather than with simple depression— the nerve-centres 
appear to be more susceptible than is normal to external impressions, 
as well as to those impulses which originate in the cerebral centres 
themselves and are connected with the emotions. As a result of this 
state arise symptoms ranging in their intensity from the simple 
state of unrest known as nervousness to the wildest convulsion of 
hysteria. It is in this class of affections that the so-called "antispas- 
modics" are useful. The drugs included in this group are nearly all 
possessed of only slight physiological power but of strong flavor, and 
it is not improbable that a large part of the benefit following their 
use is due to a psychical effect. As the diseases in which they are 
employed are associated with weakness it is believed, by some, that 
they are mildly stimulant to the central nervous system. 

MUSK. 

A highly odorous, unctuous substance, obtained from the glands 
situated just in front of the preputial orifice of the Moschus mos- 
chiferus, or musk-deer of Thibet. It is of brownish color with a very 
strong persistent odor and a bitterish taste. It is partly soluble both 
in alcohol and water, but not completely so in either menstruum. 
On account of its extraordinary high price it is very largely adulterated 
with various materials. The difficulty of obtaining pure musk and 
its expensiveness almost entirely precludes its use as a practical 
remedy. 

Official Preparations : 

Moschus 10 to 15 grains (0.6-1.0 Gm.). 

Tincture Moechi (5 per cent.) 1 to 2 fiuidrachms (4-8 C.c). 



* The term Antispasmodics, which was formerly applied to this group of drugs, has been such 
a fruitful source of confusion to the student, suggest inc. ;1 relation to the motor depressants, that 
it ha- been thought wise to drop it u- meaningless. 
14 



CALMATIVES 15 

Physiological Action. — Musk appears to act upon the nervous 
system simply as 'a mild stimulant and antispasmodic. Jorg and 
Sundelin have experimented with it upon healthy men with somewhat 
contradictory results. According to the first-named observer, twenty 
grains of it induce exhilaration without lassitude, but, according to 
the latter authority, may cause giddiness, drowsiness, and lassitude. 
Both observers noted a slight increase in the frequency of the pulse. 

Therapeutics. — Musk is at present very little used, but it 
is strongly recommended by some of the older writers in various 
spasmodic affections, especially in hysterical convulsions. In hiccough 
it has been considered a specific. In our experience, in the crisis of 
low fevers when the symptoms of nervous exhaustion are extreme 
and threaten death, musk is a very valuable remedy. Thus, in 
advanced typhoid fever a condition sometimes develops in which the 
pulse is exceedingly feeble, and the temperature has a tendency to 
rise to a great height, but yields almost immediately to the use of 
cold, only, however, to remount as soon as the cold is withdrawn. 
We have seen musk at such time control the temperature, steady 
the pulse, and apparently save life. In other cases of advanced fevers 
the powers of the system entirely give out, and the patient passes 
into a condition of collapse, with subnormal temperature, and mayhap 
coma-vigil: this state we have also seen relieved by musk. Originally 
recommended by Trousseau in the ataxic pneumonia of drunkards, 
musk may be a useful remedy in any forms of adynamic pneumonia 
when there is wild or muttering delirium. From ten to fifteen grains 
of musk (the best attainable) should be given at a dose, preferably 
by rectal injection, suspended in mucilage. The effect of the single 
dose lasts about six hours. 

VALERIAN. 

The rhizome and roots of the Valeriana officinalis. This European 
plant is an herbaceous perennial growing to the height of from two 
to four feet, with pinnately compound leaves, and small pinkish 
flowers in compound cymes. 

The official portion consists of a short, yellowish rhizome with 
numerous fibrous roots. It has a strong, disagreeable odor and a 
bitter camphoraceous taste. Valerian depends for its activity upon 
a volatile oil and the valeric acid which it contains. 

Official Preparations : 

Fluidextractum Valerianae 2 to 1 fhiidraehm (2-4 Co.). 

Tinctura Valeriana* (20 per cent.) 1 to 3 Huidrachms (4-10 C.c). 

Tinctura Valerianae Ammoniata (20 per cent.)l to 3 fluidrachms (4-10 C.c). 

Physiological Properties. — The physiological action of valerian 
is very feeble. The extraordinary excitement which it produces in 
cats is probably due to a suggestive odor rather than to any direct 
influence. Large doses of valeric acid cause in rabbits some accelera- 



16 GENERAL REMEDIES 

tion of the pulse and respiration, followed by lessened frequency of 
these functions and general lassitude. Enormous doses may produce 
a fatal gastro-enteritis. According to Butte, the extract of valerian 
has a pronounced effect in checking the destruction of glucose in the 

blood. 

I 'pon man, very large doses are said to produce a feeling of warmth 
in the stomach and quickening of the pulse, followed by nausea, 
vomiting, and colicky pains. 

Therapeutics.— Valerian is useful in the state of unrest familiarly 
known as nervousness, and is much used in the minor disturbances 
of hysteria. It has been employed, though with little advantage, 
in mania a potu and adynamic delirium as an adjuvant to more 
powerful drugs. 

Ammonium Valerate or Ammonium valerianate, a white salt in 
quadrangular plates, effloresces in a dry and deliquesces in a moist 
atmosphere, has an odor resembling valerian and a sharp, sweetish 
taste, and is very soluble in water and in alcohol. According to 
YV. E. Parke, it produces in the frog convulsions followed by general 
paralysis, both the convulsions and the palsy being of spinal origin, 
and also is capable by local contact of killing any of the higher nerve- 
tissues. These effects are probably due to the ammonia, and throw 
no light upon the therapeutic action of the drug, which is about 
equivalent to valerian, but sometimes has especial usefulness in 

• his headache. 

Anmionii Valeras 10 grains (0.6 Gm.). 

ASAFETIDA. 

An exudation obtained by incising the living root of the Eerula 
fcetida, an umbelliferous plant of Afghanistan. It occurs mostly in 
irregular opaque masses of a dull yellowish or pinkish brown, white 
when freshly broken, of a bitter acrid taste and a strong garlicky 
odor. It is partly soluble in alcohol, although insoluble in water 
and when triturated with the latter yields a milky emulsion. Asa- 
fetida is composed chiefly of gum and resin, but its properties are in 
great part due to the volatile oil, of which it contains from three 
to nine per cent. 

Official Preparations : 

Pilulffi Asafcetidse (each 3 grains) 2 to 4 pills. 

Tinctura Asafoetida? (20 per cent.) J to 1 fluidrachm (2-4 C.c). 

Ernulsum Asafoetida (4 per cent.) 4 to S fluidrachms (15-30 C.c). 

Physiological Action. — When taken into the stomach, asafetida 
acts as a local stimulant and carminative, and on this account is in 
some parts of the East used as a condiment. The oil is without doubt 
absorbed. The evidence as to its action upon healthy men is both 
scanty and contradictory. Thus, while M. Pidoux took half an ounce 



CALMATIVES 17 

in a single dose without perceptible effects other than to render his 
secretions horribly offensive for two days, Jorg and his disciples found 
that in twenty-grain doses it produced gastric uneasiness and pain 
with alvine dejections, increased the pulse-frequency and animal 
warmth, quickened the respiration, and caused headache, giddiness, 
and erotic excitement. 

Therapeutics. — Asafetida is the most efficient of the antispas- 
modics, and may often advantageously be substituted for valerian 
in functional spasm, in hysteria, and in nervousness. It differs from 
valerian in having a much more decided action upon the mucous 
membranes. It is an excellent carminative, and is constantly used 
as an enema for the relief of tympanites. It is valuable in dyspepsia, 
with flatulent colic and costiveness, of the aged or hysterical. As a 
stimulating expectorant and antispasmodic, it is useful in whooping- 
cough and in chronic bronchial catarrh, especially in old people with an 
asthmatic tendency. In infantile convulsions, in infantile colic, and 
in flatulent constipation, asafetida enemata (two to four fluidrachms 
of milk) are useful and harmless. 

SUMBUL. 

Although the U. S. Pharmacopoeia defines sumbul as the "rhizome 
and root of an undetermined plant" it is generally supposed to be 
derived from the Ferula sumbul, a large perennial plant growing in 
Central and Eastern Asia. It enters commerce in the form of brown 
pieces, one-half to two inches long and about one inch in diameter. 
The odor is musk-like, the taste at first sweet, but then bitter, and 
leaving a sensation of warmth. It depends for its activity upon the 
presence of sumbulic or angelic acid, and probably also contains 
valeric acid. 

Official Preparations : 

Extractum Sumbul 5 to 10 grains (0.3-0.6 Gm.) . 

Fluidextractum Sumbul J to 1 fluidrachm (2-4 C.c). 

Therapeutics. — Sumbul is used for similar purpose as valerian, 
but is especially valued in nervous states associated with disorders 
of menstruation. 

HOPS. 

The strobiles (fruit) of Humulus lupulus, or hop-vine, cultivated 
in Northern and Middle Europe and in the United States, are soft, 
greenish cones, one or two inches in length, composed of thin, leaf- 
like, imbricated scales, having a bitter taste and a heavy narcotic 
odor. At the bases of the scales is a yellowish powder, official under 
the name of Lupulinum. Lupulin is in minute grains, and contains, 
according to Payen, two per cent, of volatile oil, 10.3 per cent, of 
bitter principle, and fifty to fifty-five per cent, of resin. Volatile oil 
of hops is yellowish, and has a strong odor of the drug and an acrid 
2 



18 GENERAL REMEDIES 

taste. The bitter principle has been obtained by Lermer in brilliant 
rhombic columns, of an acid reaction. 

Official Preparations : 

Pluidextmctum Lupulini 15 to 30 minims (1-2 C.c). 

reeina Lupulini 5 to 15 minims (0.3-1.0 C.c). 

BTnmuliiH I to 1 drachm (2-4 Gm.). 

Hops is a bitter tonic and a very feeble narcotic, which has been 
given to quiet nervous irritability, and to strengthen digestion in 
neurasthenia, and even in delirium tremens. In abnormal sexual 
I it has been much used, but is of no value. A hop poultice 
is made by moistening with hot water the hops contained, alone or 
mixed with an equal part of Indian meal, in a gauze bag of the required 
size and shape. 

CIMICIFUGA. 

The Cimicifuga racemosa is an indigenous herbaceous plant, 
growing abundantly in shady woods, attaining a height of six or seven 
feet, and readily distinguished by its very large multi-compound leaves 
and its long-branched spikes of whitish polyandrous flowers, naked 
when open. The official portions consist of a knotted head, with 
numerous fine, brittle rootlets; the odor is faint, and the taste bitterish, 
somewhat astringent and acrid. The nature of its active principle 
has not been determined. The tendency of the drug to deteriorate 
on keeping indicates the presence of a volatile principle. 

Official Preparations : 

Extractum Cimicifugae 5 to 15 grains (0.3-1.0 Gm.). 

Fluiclextrartum Cimicifugae 20 to 60 minims (1.2-4.0 C.c). 

Tinctura Cimicifuga (20 per cent.) 1 to 2 fluidrachms (4-8 C.c). 

Physiological Action. — There have been no cases of poisoning by 
cimicifuga, but large doses produce giddiness, intense headache, 
general prostration (evidences that it has influence upon the cerebrum), 
with reduction of the pulse-force and rate, and occasionally vomiting, 
but the emetic action is never violent. Hutchinson found that large 
doses acted on frogs as a depressant of the sensory side of the spinal 
cord, producing complete anesthesia with loss of reflex activity at a 
time when voluntary movement was still preserved, the development 
of the anesthesia not being prevented by shutting off access of the 
poison from the peripheral nerves by tying the arteries of the leg, 
and both motor nerves and muscles being found after death func- 
tionally active. Upon the circulation cimicifuga acts as a depressant, 
producing in the mammal fall of the arterial pressure and slowing 
of the pulse, and causing finally diastolic arrest of the heart. As 
the slowing of the pulse is not prevented by previous section of the 
vagi, and as the isolated frog's heart becomes slow and in a little 
while paralyzed after direct contact with the cimicifuga, it is evident 
that the drug acts as a direct depressant to the heart-muscle; but, 



CALMATIVES j«) 

since Hutchinson found that asphyxia is incapable of causing rise of 
pressure while the heart is still beating strongly, it is probable that 
it not only depresses the heart but also the arterial system. Under 
the influence of the drug the respiration becomes slow and suffers 
final arrest. 

Therapeutics. — Cimicifuga was originally proposed by Young in 
1831 as a remedy in chorea, and in the simple chorea of childhood its 
value is unquestionable. It must be given until it produces physio- 
logical effects, and in most cases the consentaneous exhibition of iron 
and laxatives materially aids it. We have seen it promptly cure 
urticaria of nervous origin after complete failure of the usual treat- 
ment. In acute inflammatory rheumatism cimicifuga has been highly 
recommended, but is at present very rarely, if ever, used. In chronic 
bronchitis it is sometimes employed with asserted benefit when there 
is free expectoration. 

Cypripedium is the rhizome and roots of Cypripedium hirsutum 
and Cypripedium parviflorum, to which are attributed tonic, dia- 
phoretic, and antispasmodic properties. They are said to contain a 
volatile oil but no alkaloids. 

Cypripedin of the drug stores is an impure oleoresinous substance, 
the dose of which is given as from one-half to three grains. Cypri- 
pedium is especially recommended for the allaying of functional 
nervous excitability and in hypochondriasis. The fluidextract, 
Fluidextractum Cypripedii, may be given in doses of fifteen to 
thirty minims (1-2 C.c). 

Acetic Ether {Mther Aceticus) is a transparent, colorless, some- 
what fragrant liquid, containing about ninety per cent, of ethyl acetate. 
It has been used to a slight extent in medicine as a stimulant and 
calmative. It resembles ordinary ether somewhat in its action, but 
is less volatile and less rapidly absorbed and eliminated. It is capable 
of producing anesthesia, but is in every respect much slower and less 
certain in its action than ordinary ether, and is practically of no 
value. Dose, internally, fifteen minims (1 C.c). 

Lactucarium. — The concrete juice of the Lactuca virosa,* or 
garden lettuce, occurs as a dark reddish-brown to a light yellowish, 
hard extract, having a faintly narcotic odor and bitter taste. A pecu- 
liar soothing, hypnotic influence has been attributed to it, but its 
activities are so feeble that in a number of trials with very large doses 
we have been unable to- perceive any effect whatever. According 
to Fronmuller, lactucin is even less active than the crude drug. In 
France lactucarium is used locally as a narcotic demulcent in the 
treatment of diseases of the throat. 

* For a case of reputed poisoning by Lactuca virosa, see Schmidt's Jahrb., clxxi. 137. 



20 GENERAL REMEDIES 

Official Preparations : 

Tinctura Lactucarii (50 per cent.) 1 to 2 fluidrachms (4-8 C.c). 

Syrupus Lactucarii (10 per cent.) i to 1 fluidounce (15-30 C.c). 



REFERENCES. 

VALERIAN. CiniCIFUGA. 

Hittk C. K. B. B.. 1891, iii. Hutchinson Th. G., 1887, 731. 

Kionka D. M. W., Dec. 1901. Young A. M. J. S., 1831, ix. 

Parki Th. G., 1887, 167. 

BcHWEBSENsra Tli. M., 1897. LACTUCARIUM. 

I'honmulleb Deutsche Klinik, 1805. 



FAMILY II.— ANESTHETICS. 



The term Anesthetics is here employed as the name of a group of 
volatile substances, whose vapor has the power of producing loss of 
consciousness, preceded by or accompanied with loss of sensibility 
and diminished muscular action. The medical properties of these 
substances are largely due to their volatility, by virtue of which they 
are very rapidly absorbed and almost as rapidly eliminated by the 
mucous membrane of the lungs. As a consequence of this, their 
action is easily controlled. 

A very large number of theories have been brought forward to 
account for the peculiar effects of anesthetics; of the more important 
of these theories an elaborate discussion may be found in the tenth 
edition of this work. There is, however, nothing more mysterious in 
the action of ether and chloroform upon the nerve-centres than there 
is in the influence of opium or strychnine upon these centres, the 
influence of the anesthetic being as certainly direct and vital as is 
that of any other drug which acts upon human organs or tissues. 

The action of anesthetics may be modified by the injection of 
narcotics. Morphine given hypodermically about half an hour before 
the exhibition of the anesthetic is said to have a decided effect in 
prolonging the anesthesia. Chloral administered shortly before etheri- 
zation certainly causes the first stages of the latter to be much quieter 
than usual, and also prolongs the narcosis. Some years since 
Neudorfan introduced into Berlin the use of oxygen gas with chloro- 
form in the production of anesthesia; more recently the method has 
been revived in America.* It has even been asserted that the oxygen 
increased the anesthetic effect of the chloroform. There is not at 
present writing sufficient evidence, however, of the value of the 
method. 

The chief purposes for which anesthetics are used are to relieve pain 
and to relax spasm. To meet the first indication they are employed 
by surgeons especially; but they are also exceedingly valuable in 
cases of suffering from disease. It must be borne in mind that their 
action is transitory and is accompanied by more or less disturbance 
of the general system, and that consequently they are to be employed 
only when the pain is exceedingly severe and transient. To relieve 
pain, anesthetics are used with great propriety during childbirth. t 
In normal labor it is not commonly necessary to produce complete 

* See Boston Med. and Surg. Journ., 1896, and New York Med. Record, 1896. 

t We see no reason for believing that anesthesia of the mother seriously influences the child 
and do not think that much weight can be attached to the assertions of Hofmeier (Berlin. Klin. 
Wochensch., 1883, xx. 230) that there is produced an increased elimination of nitrogen in the 
new-born babe. 

21 



22 GENERAL REMEDIES 

anesthesia. When the full effect of either ether or chloroform is 
induced, there is almost always a weakening, and very often an aboli- 
tion, of the uterine contractions. The anesthetic should be adminis- 
tered in such quantities as to relieve the pain without decidedly 
interfering with the muscular spasm. In certain cases this can be 
done, in others it is impracticable. We have obtained advantageous 
results in some cases by suspending the pains for about half an hour 
by means of ether, and then entirely withdrawing the anesthetic. 
By this treatment the weak, painful, ineffectual efforts of a worn- 
out, nervous patient may often be converted into regular, successful 
efforts. The risk of post-partum hemorrhage is materially increased 
by anesthetics, so that it is well to administer, after their use, two 
drachms of the rluidextract of ergot as soon as the perineum is well 
distended by the child's head.* Anesthetics are frequently used in 
surgery for the purpose of relaxing spasm, as in cases of dislocation, 
hernia, etc. In medicine they have been employed in various forms of 
convulsions, and are especially valuable in severe hysterical convul- 
sions, in puerperal eclampsia, and in spinal convulsions; in epilepsy 
they are very rarely called for; in infantile convulsions they may be 
sparingly used when the convulsion itself threatens life. In various 
spasms of the excretory dticts or canals, and especially during the pas- 
sage of calculi, they act very favorably, both by relieving pain and 
by producing relaxation. In asthma, and in spasmodic stricture of 
the msophagus, as in all other cases of oft-repeated spasm, they 
should be administered only to meet temporary indications, as their 
habitual use is deleterious. 

NITROUS OXIDE. 

Nitrogen Monoxide (N 2 0) is a colorless, almost inodorous, gas, of 
a sweetish taste. It is a very active supporter of combustion. Water 
absorbs nearly its own bulk of it. It is made by the distillation of 
ammonium nitrate, which resolves itself into the gas and water. 
Nitrous oxide gas is now supplied in condensed form. In making 
nitrous oxide the temperature should never be allowed to rise above 
482° F., for fear of generating nitric oxide. 

Physiological Action. — The inhalation of pure nitrous oxide 
gas is followed in from a half to three minutes by unconsciousness, 
which usually comes on quietly, but is sometimes preceded by hilari- 
ous, erotic, or pugnacious excitement. During the anesthesia the 
face presents a bloated, swollen, intensely livid appearance. 

The question whether nitrous oxide produces anesthesia through 
inherent properties of its own, or whether it acts simply by shutting 
off oxygen, has been much discussed. The intoxicating effects of 
mixtures of nitrous oxide and oxygen, although complete anesthesia 
may not result, show that the gas has a direct action on the brain. 

* Deaths from anesthetics are very rare during parturition, but have occurred. (See C. B. 
Vanzant, Cincinnati Lancet, 1893, xxx.) 



ANESTHETICS 23 

Moreover, Paul Bert has shown that a mixture of nitrous oxide and 
oxygen, under pressure, will produce complete anesthesia. For these 
and other reasons it is, to-day, generally conceded that nitrous oxide 
is capable of producing anesthesia by virtue of its own inherent 
action on the nerve-centres. Nevertheless, the narcosis ordinarily 
produced is due not only to the nitrous oxide but also in part to 
asphyxiation. The evidence on both sides of this discussion is briefly 
summarized in small type below. 

It is well established that nitrous oxide will not support life. A taper will burn 
in it, it is true, but the liberation of oxygen is due to the high heat, and at 
the temperature of the body nitrous oxide is a stable compound. 

In 1864 Ludimar Hermann, as the result of his experiments, came to the con- 
clusion that the addition of oxygen to nitrous oxide puts an end to its anesthetic 
properties, and that it acts simply as an asphyxiant. In 1873 Jolyet and Blanche 
arrived at. a like opinion as they found that animals breathing an air containing 
sixty to eighty per cent, of nitrous oxide and twenty to forty per cent, of oxygen 
are unaffected; analyses of the blood of two dogs yielded the following results: 

No. 1. Conscious. No. 2. Unconscious. 



Carbonic acid 46 per cent. 

Nitrous oxide 29 per cent. 

Oxygen 19.7 per cent. 



Carbonic acid 36.6 pe^r cent. 

Nitrous oxide 34.6 per cent. 

Oxygen 3.3 per cent. 



The statements of the French observers just quoted have been abundantly 
corroborated by the observations of various subsequent investigators. Colton, 
Elihu Thomson, and H. C. Wood have separately and repeatedly demonstrated 
that animals will live no longer in nitrous oxide than they will in an atmosphere 
of hydrogen or nitrogen, or even in a vacuum. In a long series of experiments, 
H. C. Wood determined that the introduction of minute quantities of oxygen into 
nitrous oxide prolonged the time necessary for the production of anesthesia in 
direct proportion to the percentage present, ten or even eight per cent, of oxygen 
suspending entirely the anesthetic action of nitrous oxide gas upon the dog. The 
average time required for the production of anesthesia was nearly doubled by the 
addition of three per cent, of oxygen, and increased more than twelvefold by the 
use of five per cent, of oxygen. Thomson asserts that the inhalation of pure nitro- 
gen produces symptoms similar to those of nitrous oxide narcosis. In conformity 
with this are the researches of C. A. MacMunn and Amory; the former observer 
finding that when an animal is killed by nitrous oxide the arterial blood gives only 
spectrum lines of reduced hemoglobin, while after death from chloroform the lines 
of oxyhemoglobin are very apparent. 

H. C. Wood found that the inhalation of nitrous oxide is usually followed by 
a rise of the arterial pressure, accompanied by a great disturbance of the pulse; 
the pulse at first becoming irregular and tumultuous, but by and by settling, so that 
when anesthesia is complete the pulse-wave is remarkably large and full and the 
rate very slow. The rise and fall of the arterial pressure in nitrous oxide anesthesia 
was found to vary remarkably, not only in different inhalations, but at different 
periods of the same inhalation. Amory has found, in experiments upon the 
dog, that there is, during the anesthesia, increased blood-pressure in the cerebrum, 
with stasis in the capillaries. These results show that the circulatory phenomena 
produced by nitrous oxide resemble those of mechanical asphyxia as closely as 
could, a priori, be expected. 

Martin Goldstein found that when he put frogs in an atmosphere of pure nitrous 
oxide they became motionless, with a complete loss of the reflexes, in fifteen min- 
utes; while when they were put in an atmosphere of nitrogen or some other in- 
different gas they preserved their irritability for some hours. It is known that 
while the nervous system of the mammal requires for its activity the presence of 



ji GENERAL REMEDIES 

oxygen, the nervous system of the frog remains functionally active for some hours 
all circulation— that is, after all carrying of oxygen to it— has ceased. 

Believing that if he could increase the amount of nitrous oxide in the blood he 
oould gel an anesthetic action from it, Paul Bert experimented by exposing the 
animal in a chamber having air so compressed that the pressure was at least that of 
two atmospheres, and found that under these circumstances he could obtain anes- 
thesia with a mixture of eighty-five per cent, of nitrous oxide and fifteen per cent, 
of oxygen, but thai when nitrogen was substituted for nitrous oxide no anesthesia 
was produced. Bert's method was for a time employed for the purposes of sur- 
gical anesthesia in Paris and in some other capitals of Europe, the clinical records 
showing that it is possible to produce anesthesia with the gas in the proportion named 
above. Practically, however, the necessary apparatus was found to be too cumber- 
some and expensive for use. In 1881 Klikovitch, of St. Petersburg, used with 
alleged BUCcess in parturition Paul Bert's mixture of gases without pressure. 

In 1891 Nan Arsdale found that it was possible in rare cases to produce anes- 
thesia in the human being with mixtures of oxygen and nitrous oxide in the propor- 
tion of fifteen to eighty-five per cent., and that in many cases a mixture in 
the proportion of ten to ninety per cent, would produce a moderately complete 
anesthesia without cyanosis. 

In a research extending over three years, F. W. Hewitt corroborated the as- 
sertions of Van Arsdale, finding that it is possible, in some cases at least, to produce 
deep and satisfactory anesthesia, without obvious asphyxial manifestations, by 
mixtures of nitrous oxide and oxygen containing even as much of the oxygen as 
is present in our atmosphere. George T. Kemp made a series of experiments, 
some of which seem to be very decisive. Thus, an animal having been anesthetized 
with nitrous oxide, a slit in the canula was adjusted so that it let in just sufficient 
air to keep the animal alive and anesthetized. When nitrogen was substituted for 
nitrous oxide, the amount of air remaining the same, the dog gradually came out of 
his anesthesia. Experiments with the blood showed that, though at times perfect 
anesthesia existed with as high a percentage of oxygen in the blood as 16.8, it 
usually was 8.5, and sometimes not until the percentage was reduced to 7.9. For 
reasons given in his paper, which we cannot go over here, Kemp believes that with 
this amount of oxygen metabolism remains about normal, a conclusion, however, 
which the evidence he brings forward hardly proves. 

If nitrous oxide, as the evidence at present indicates, is capable of 
producing unconsciousness by virtue of its inherent properties, it 
must act upon the cerebrum, but it is remarkably inert in regard to 
other portions of the organism. The chief evidence as to its influence 
upon the spinal cord is that of Goldstein, that it diminishes the reflexes 
in frogs. That its action on the spinal cord is very feeble seems to 
be shown by the fact, which has been repeatedly asserted, that 
in human beings the conjunctival reflexes often persist after deep 
anesthesia has been produced. 

The experiments of Waller and of Amory show that nitrous oxide 
does not affect the motor nerve trunks. Ulbrich believes that it 
produces alterations in the blood, but Hermann, Jolyet and Blanche, 
Goldstein, MacMunn, Buxton, and Halliburton are in accord with 
Kemp in asserting that it does not make any compound with hemo- 
globin. Further, Kemp is in accord with H. C. Wood's experiments 
in showing that it has no definite influence upon the heart or the 
arteries. 

Therapeutics. — Of all the anesthetics, nitrous oxide is the safest. 
It is probably administered to more than seven hundred and fifty 



ANESTHETICS 25 

thousand persons yearly, and yet only four recorded deaths are cer- 
tainly attributable to it.* The opinion of Cartwright and of W. Ottley, 
that in cases of heart disease permanent increase of the cardiac weak- 
ness is caused by nitrous gas inhalation, is not established. The 
final fall of blood-pressure produced by the gas was found in the 
experiments of H. C. Wood to be due to paralysis of the vaso-motor 
apparatus, probably of asphyxial origin, and death always occurred 
from respiratory paralysis, the heart continuing to beat powerfully 
after respiration had ceased and the arterial pressure had fallen 
very low. Even when alarming symptoms occur during nitrous oxide 
anesthesia, the results are very rarely disastrous, because the loss of 
function has been due, not to the presence of a poison, but to the 
absence of oxygen, and although the paralysis may be complete, the 
life-power sleeps before it dies, and is ready to react to oxygen. 
Immediate artificial respiration is the one remedy for the treatment 
of alarming symptoms during nitrous oxide asphyxia. 

In diseases of the kidney nitrous oxide is probably far safer than 
any of the liquid anesthetics, since in the experiments of Thomson 
and Kemp it was found to have no other effect upon the kidneys than 
that which it exerted upon the general circulation. Experience has 
not confirmed the assertion of Lafont, that nitrous oxide anesthesia 
is prone to be followed by miscarriage, chlorosis, and epilepsy. His 
especial warning against the production of diabetes mellitus, and his 
statement that glycosuria may be produced by the drug in the dog, 
remain unconfirmed by clinical or experimental evidence, although a 
well-known Philadelphia surgeon persistently attributed his own 
fatal diabetes to the use of nitrous oxide. In experiments made by 
George S. Woodward and Alfred Hand in the laboratory of the Uni- 
versity of Pennsylvania it was found impossible to produce glycosuria 
in the dog. On account of the high blood-pressure with venous 
stasis which occurs during nitrous oxide anesthesia, atheroma or 
other diseases of the arterial walls should be considered a contra- 
indication to the use of the gas, and fatal apoplexyf has occurred 
during or immediately after its administration. 

Administration. — The difficulty with the practical use of nitrous 
oxide for other than the brief anesthesia required in teeth extraction 
and other forms of minor surgery has been the extreme fugaciousness 
of the anesthesia, as well as the asphyxial symptoms always present. 
It is affirmed that these difficulties are overcome by the consentaneous 
use of oxygen with the gas. Undoubtedly the asphyxial symptoms 
are greatly lessened, but the allegation that the period of recovery 
after the withdrawal of the gas is distinctly prolonged has not, in 
our experience, been sustained. In various cases we have noticed 
the return to consciousness as complete in from twenty-eight to forty 



* Not including the case reported in the Dental Cosmos, June, 1872. (See Brit. Journ. Dent. 
Set., Feb. 1873; Brit. Med. Journ., 1877, i. 400; Ibid., 1883, ii. 729; Dent, and Surg. Microcosm, 
Oct. 1895.) In one of these cases the result is said to have been due to syncope. 

t See Dental Cosmos, 1890; also Therap. Gaz., 1896, xii. 



•_>,; GENERAL REMEDIES 

seconds. With great care in the administration of the mixed gases, 
the anesthesia can be, it is true, almost indefinitely prolonged, but the 
danger of recovery at any moment is great. It is common for operators 
to vary the percentage of oxygen according to the appearance of the 
patient, often giving first pure nitrous oxide and adding oxygen 
without any definite measurement when the asphyxial symptoms set 
in; watching the effect of the oxygen and increasing or lessening it 
according to the facial expression of the patient. Matthew H. Cryer, 
of the University of Pennsylvania Dental Faculty, states that the 
apparatus prepared in London according to Hewitt's plan is impracti- 
cable owing to the fact that an easy reflux is afforded for the two 
gases into each other, and has worked out an apparatus which seems 
to be satisfactory and is not over-cumbersome. The method is 
certainly a distinct advance, in that it enables the operator at any 
moment to have the subject breathe pure oxygen if disagreeable 
symptoms occur. 

Nitrous oxide is sometimes used in conjunction with ether, the 
primary anesthesia of nitrous oxide allowing the patient to pass under 
the ether without the unpleasant excitement. Le Breton is probably 
correct in his belief that this method is safer than ether alone, because 
of the smaller amount of ether required. 

ETHER. 

Ethyl oxide [(C 2 H 5 ) 2 0] is a colorless, volatile liquid, obtained by 
the dehydration of alcohol by sulphuric acid. It is very inflammable, 
as is also its vapor, which is two and a half times heavier than air. 
It is freely soluble in alcohol, and is itself a powerful solvent. Its 
odor is strong and peculiar; its taste is hot. Its specific gravity, 
when pure, is 0.713, and its boiling point 95° F. Ether of the U. S. 
Pharmacopoeia contains ninety-six per cent, of ethyl oxide, and 
should boil "when a test-tube, containing some broken glass and 
half filled with it, is held for some time closely grasped in the hand." 

Official Preparations : 

.It her 15 to 60 minims (1-4 Co.). 

Spiritus .Etheris (32 per cent.) i to 2 fluidrachms (2-8 C.c). 

Spiritus .Etheris Compositus [Hoffman's 

Anodyne] (Ether 325, Ethereal oil* 25, 

Alcohol 650) J to 2 fluidrachms (2-8 C.c). 

Although ether had been known chemically for many years and 
had even been employed in the treatment of pulmonary affections 
the credit of introducing it as a general anesthetic belongs to 

* When alcohol is distilled with an excess of sulphuric acid there is found a substance com- 
monly known as heavy oil oj wine; this when mixed with an equal volume of ether constitutes 
Oleum AZthereum. of the U. S. Pharmacopoeia. 

Heavy oil of wine is a substance of little power, but Hare has shown that large doses are 
primarily stimulant to the vaso-motor centres and later, if the quantity is sufficient, dilate the 
vessels and weaken the heart. It is improbable that the presence of this compound affects the 
action of Hoffman's anodyne, whose virtues as a carminative and calmative are due chiefly to 
the ether. 



ANESTHETICS 27 

W. T. G. Morton, a Boston dentist, who employed it in his practice 
in 1846, and later called it to the attention of Dr. Warren, who per- 
formed the first surgical operation under artificial anesthesia in the 
same year. 

Physiological Action. — Locally, ether is a violent irritant; it 
is absorbed with rapidity through the mucous membranes both of 
the lungs and of the gastro-intestinal tract. When taken freely it is 
eliminated largely unchanged by the lungs. 

Upon the lower animals ether acts as upon man, and it has 
been shown by Claude Bernard that the most primitive infusoria are 
susceptible to its influence. 

Nervous System. — Both in man and the lower animals the cerebral 
functions are the first to be affected by ether; the order of the involve- 
ment is — first the cerebrum, next the sensory centres of the cord, 
next the motor centres of the cord, next the sensory centres of the 
medulla oblongata, and finally the motor centres of the medulla 
oblongata. The nerve trunks can be paralyzed by the direct applica- 
tion of ether vapors, but this probably does not occur in the living 
animal. 

According to the experiments of H. C. Wood, Jr., when the ether is given in 
such a manner to the dog as to avoid all violence of administration, and in minute 
dose, the first positive indication of the loss of intellection is failure of the percep- 
tion and interpretation of sound, the sense of sight lasting somewhat longer. _ Loss 
of coordination and loss of motor power, though with a continuation of movement, 
are the next phenomena. It was further demonstrated in these experiments that 
there is a stage of ether narcosis in which the sensibility is distinctly lessened, al- 
though no motor changes are demonstrable. This affords confirmation of the early 
experiments of Flourens, who found that the order in wliich during etherization the 
power of responding to pricking is lost was, first, in the posterior or sensory portion 
of the spinal centres; second, in the anterior or motor portions of the spinal cord; 
and, third, in the medulla oblongata. Longet has confirmed this order, except that 
by using powerful galvanic currents he was able, even in the deepest narcosis, to 
get a response from the anterior portion of the cord. 

Wright has demonstrated histological changes in the pyramidal cells of the 
nervous centres due to the administration of ether or chloroform. The more 
prolonged the exposure to the anesthetic, the slower is the return to the normal. 

Waller found that if he brought dilute ether or chloroform vapor in direct 
contact with a motor nerve, that nerve lost its power of transmitting electrical 
impulses. If the vapor had not been too concentrated, the nerve recovered its 
function after removal of the anesthetic. The recovery after chloroform was less 
rapid than after ether. If the observations of Longet and Serres be correct, the 
sensory nerve-fibres are more susceptible to the influence of ether than are the 
motor. They found it possible, however, by the direct application of ether to a 
nerve, to produce a condition in which pinching the nerve below the point of appli- 
cation caused no pain, although voluntary movement was preserved, and galvaniza- 
tion of the nerve trunk above the point of application induced spasms in the tributary 
muscles, — i.e., the power of conducting an impulse downward was preserved, that 
of conducting it upward was lost. By a longer application of the anesthetic the 
function of the efferent as well as of the afferent fibres was abolished, temporarily 
at first, but, if the application were .persisted in, permanently. 

Conly found that in animals killed by ether, chloroform, or chloral, the motor 
nerves and muscles preserve their function longer than in animals killed by sudden 
violence. Nevertheless, F. S. Locke found that in the frog, at least, the muscles 



2 8 GENERAL REMEDIES 

me directly affected by etherisation; there being not only a lessening of the height. 
*„,- ^ contraction under stimulation, but also an alteration in its form. 

Qnon the motor system of organic life ether certainly acts, but much less ener- 
wticauy than upon the voluntary system. Thus, after death from ether the ver- 
mi.ular" movementa of the intestine, although less active than normal, are very 
rarely, if ever, entirely absent. 




Circulation.— The first effect of ether is usually to cause a rise in 
the arterial pressure, which may be maintained even through a pro- 
longed ether narcosis, and may continue until manifest failure of 
respiration; usually, however, it is after a time succeeded by a fall 
of pressure. Blauel found, in tonometrical studies upon man, that 
during ether anesthesia the pressure is raised in seventy-nine per 



ANESTHETICS 29 

cent, of t he cases, not affected in nine per cent., lowered in twelve; 
per cent. What evidence we have upon the subject indicates that 
the primary action of ether upon the heart is that of a stimulant, 
though later if in sufficient amount it undoubtedly acts as a cardiac 
depressant ; that this depressing action is feeble, is shown by the 
experiments of Tunnicliffe and Rosenheim, who found that in the 
excised mammalian heart two per cent, of ether in the blood did not 
stop the heart. 

The rise of blood-pressure appears, however, not to be entirely 
cardiac, since Sansom found that the vessels of the frog's web are 
thrown into a persistent spasm by the inhalation of ether; and 
Bowditch and Minot conclude as the result of their experiments 
that in the mammal the drug first stimulates, afterwards depresses, 
the vaso-motor centres. 

Blood. — It is frequently asserted that ether when added to blood 
coagulates it. A. Schmidt, however, states that the coagulation is 
due to ozone which has been generated in the ether, since freshly 
distilled ether does not coagulate albuminous substances. 

The researches of Wittich and of A. Schmidt have shown that 
when ether is added to the blood of horses, cats, or rats, the red cor- 
puscles disappear in a very short time, and, as their stroma cannot be 
demonstrated by the aid of reagents, this disappearance is due to 
its solution. The oxyhemoglobin thus set free is dissolved in the 
serum, but the presence of the ether soon causes it to crystal- 
lize. There is no proof that these changes occur to any extent 
when ether is inhaled; and the usual rapid recovery from the effects 
of the anesthetic indicates that there is no profound alteration 
of the blood. 

An imperfect study by Harley of the effect of ether on the gases 
contained in drawn blood indicates that ether does not exert much 
influence upon their proportional amounts. It is, however, quite pos- 
sible that a more thorough investigation would give a different result.* 

SUMMARY. — Locally ether is a violent irritant. In excess it 
probably depresses all higher tissues, but it especially acts upon, 
first, the cerebrum, next upon the sensory, and then upon the 
motor side of the spinal cord. It usually produces death by as- 
phyxia, due to depression of the respiratory centres. Its first ac- 
tion upon the circulation is that of a stimulant to the heart, and 
perhaps also to the vaso-motor centres. The large dose finally 
depresses both heart and blood-vessels. 

Therapeutics. — For a discussion of the use of ether as an anes- 
thetic, see Practical Anesthesia, page 37. 

Ether has been administered by the mouth in the treatment of 
colic; for this purpose the compound spirit of ether is usually to be 
preferred. It has also been employed as an anthelmintic against the 

* For literature, cases, and discussion, see Schulz, Deutsch. Milit'dr. Zeitsch., 1903, xxxii. 



30 GENERAL REMEDIES 

tapeworm, but is inferior to other remedies. It is occasionally em- 
ployed in the treatment of various nervous conditions, as neuralgia, 
hysteria, hiccoughs, and the like. 

Ether lias also been used as a cardiac stimulant in the treatment 
of syncope, shock, and other conditions in which a rapidly acting 
remedy is required; for this purpose it is usually given hypoder- 
matic-ally, its value, however, is doubtful. 

When ether is swallowed, it produces a sense of strangulation and 
choking which seriously interferes with its use. For this reason, it is 
often given in capsules, or in ice-cold water. Probably large doses 
arc best administered by putting them, mixed with an equal amount 
of brandy, on finely cracked ice before drinking. 

CHLOROFORM. 

Chloroform, which was discovered in 1831 by Samuel Guthrie, 
of Sackett'a Harbor, New York, has the formula CHC1 3 and is gener- 
ally regarded as a trichlormethane. It is produced by the action of 
chlorine upon alcohol. It is a colorless, limpid, and neutral fluid, 
with a specific gravity of 1.476. Although practically non-inflam- 
mable, it can be made to burn with a greenish flame. Its taste is 
hot and sweetish, its odor fragrant and peculiar. It is soluble in 
alcohol and in ether, but almost insoluble in water. The U. S. Pharma- 
copoeia requires that chloroform should contain, by weight, 99 to 99.4 
per cent, of absolute chloroform and 0.6 to 1 per cent, of alcohol. 

Official Preparations: 

Chloroformum 15 to 30 minims (1-2 C.c). 

Spiritus Chloroformi (6 per cent.) 1 to 2 fluidrachms (4-8 C.c.V 

Emulsum Chloroformi (4 per cent.) 2 to 4 fluidrachms (8-15 C.c). 

Aqua Chloroformi (Saturated Solution, 

about £ per cent.) 4 fluidrachms (15 C.c). 

Linimentum Chloroformi (30 per cent.) . . . .External Use Only. 

Physiological Action. — Local Effects. — Although somewhat of 
an anesthetic, chloroform applied locally is a powerful irritant. On 
the skin it produces redness and burning; if the evaporation be 
restrained vesication will be induced by it. Taken into the mouth, 
it causes a burning sensation, and, when swallowed, a sense of warmth 
in the stomach. According to both Strassmann and Salkowski it 
is an active germicide. The latter author as well as Bertels finds that 
it checks the activity of pepsin and other ferments. 

Absorption and Elimination. — Chloroform is rapidly absorbed 
through the mucous membrane of the respiratory and digestive 
apparatus. Its exact fate in the body is at present unknown. It is 
certainly eliminated, at least in part, unchanged in the expired air 
after administration by the mouth (Benedicenti) ; and after its inhala- 
tion has been detected by Fubini, by Siolfatti and by Nicloux in the 
urine. It is probably, however, in part decomposed in the system, 
since A. Zeller has found that the chlorides of the urine are nearly 
doubled bv its inhalation. 



ANESTHETICS 31 

The vapor of chloroform, when inhaled, produces symptoms 
seemingly similar to those induced by ether, except that the choking 
sensations are absent, and that the stage of excitement is generally, 
but not always, shorter and less violent than is that of etherization. 

Nervous System. — The experiments of Holmgren, Kratschmer, 
H. C. Wood, Jr., and others have demonstrated that the action of 
chloroform upon the nervous system is entirely parallel to that of 
ether (see page 27), the difference being simply one of intensity of 
•power. In practical anesthesia the stage of excitement is usually 
much less severe with chloroform than with ether, but, according to 
H. C. Wood, Jr., this hyperexcitation depends largely upon the ether 
vapor being too concentrated; when the anesthesia was induced in 
animals slowly with a very small percentage of ether in the air, the 
stage of excitement was greater with chloroform than with ether. 
The motor disturbances seen early in chloroformization, as in etheri- 
zation, have been supposed to indicate a condition of spinal stimula- 
tion, but have been shown by Bert to be of purely psychical origin. 

Bernstein found that there was no perceptible difference in the 
conducting power of the two ischiatic nerves of a frog chloroformed 
after one of its iliac arteries had been tied. 

Circulation. — When chloroform vapors are inhaled in a concen- 
trated form the first effect is a marked slowing of the pulse and rapid 
fall of blood- pressure. Dogiel believes that this is due to a stimulation 
of the inhibitory centres, because he has found that it does not occur 
after section of the vagi. Death has frequently occurred from chloro- 
form after the inhalation of a few whiffs of vapor. The theory was 
suggested many years ago that the cause of cardiac arrest is irritation 
of the respiratory mucous membranes, producing a fatal cardiac 
inhibition; a conclusion which reached confirmation in the observa- 
tions of Embley, who found that when inhalations of chloroform of 
the strength of two per cent, and upward have been given and the 
blood-pressure has fallen, stimulation of the vagi with the faradic 
current fatally inhibits the heart. The after-increase in the rapidity 
of the pulse appears to be due, at least in part, to paralysis of the 
inhibitory centres, upon which chloroform seems to act as upon the 
oculo-motor centres, producing in them at first excessive functional 
activity, but afterwards functional paralysis. Both Kratschmer and 
Knoll have noticed in rabbits, when either ether or chloroform is 
inhaled through the nose, a momentary rise of arterial pressure 
corresponding to an arrest of respiration, and, like, it, evidently 
produced by irritation of the peripheral trigeminal branches. 

As was first proved by the English Chloroform Committee, after 
the first half-minute of the inhalation of chloroform, as ordinarily 
administered, there is a progressive lowering of the arterial pressure. 
This has been confirmed by all observers on the lower animals, and 
Blauel has shown by tonometrical experiments that the same phe- 
nomenon occurs in man. There has been much dispute as to the cause 
of this fall, — whether it is of cardiac or vascular origin. There is 



32 GENERAL REMEDIES 

to-day, however, no longer any room for doubt but that chloroform 
is a direct depressant to the heart-muscle. Indeed there is strong 
evidence that, in moderate quantities, it is stimulant to the vaso- 
motor (ciitrcs although after large doses the vaso-motor mechanism 
is completely paralyzed. 

Injected into the jugular vein, chloroform instantly arrests the heart's action 
and destroys its muscular irritability.* Even the vapor of chloroform, when locally 
applied to the exposed heart, paralyzes it. When artificial respiration is main- 
tained, the effect of chloroform is very apparent. By a very ingenious series of 
experiments, MucWilliam has proved that very early in chloroform anesthesia 
there is a marked diminution of the force of the auricular and the ventricular beats, 
accompanied by dilatation of the cardiac chambers, due to the direct influence of 
i he ( hloroform. Tunnicliffe and Rosenheim, using the method of Locke, found that 
1 to 2.5,000 in the blood of chloroform notably affected the heart, and Schafer and 
Scharlieb have reached similar results. In the experiments of E. H. Embley, made 
in the method of Hering upon the mammalian heart isolated from nervous and 
respiratory influences, it was determined that the heart is so sensitive to the vapor 
of chloroform that 0.8 per cent, in the blood will produce paralysis in sixteen minutes, 
and with two per cent., arrest occurs in one minute and twenty-five seconds. 

In an elaborate series of experiments, Sherrington and Sowton found that the 
heart-muscle rapidly takes up chloroform from the blood-vessel, the tension or 
amount of the chloroform in the muscle depending not upon the length of time of 
exposure but upon the percentage of chloroform in the fluid circulating in the coro- 
nary arteries; it was further determined that the presence of the chloroform in the 
muscle is accompanied by depression of function, and that when the percentage is 
great muscular paralysis occurs. The thought naturally arises from this research 
thai sudden death may occur during chloroform anesthesia from the momentary 
sudden increase of the percentage of chloroform in the blood. 

The only experiments with which we are acquainted, to which any weight 
should be attached, as indicating that chloroform primarily paralyzes the vaso- 
motor centres, are those published as long ago as 1874 by H. P. Bowditch and 
C. S. Minot. In these experiments, which were made upon curarized animals, 
"irritation of the saphena nerve caused a much less marked rise of blood-tension 
than when the anesthetic was not used. Sometimes there was absolutely no rise 
of tension to be observed, while at other times the rise was from one-third to one- 
half that produced by the same irritation on an animal not subjected to the action 
of chloroform." Further, compression of the carotid in the chloroformed animal 
did not cause the customary spasm and rise of arterial pressure. 

It must be remembered that chloroformization interferes with the functional 
activity of the sensory side of the nervous system, so that an impulse produced by 
irritation of the sensitive nerve fails to reach the vaso-motor centres in full force. 
In many of the experiments of Bowditch and Minot, irritation of the saphenous 
nerve produced distinct rise of pressure, showing that the vaso-motor centre was 
not paralyzed, though the arterial pressure had fallen very distinctly. 

On the other hand Sansom and Harley state that there is a spasm of the small 
vessels, which can be readily seen to occur in the web of the frog during chloroformi- 
zation. Not until the third stage is reached, according to these authors, do the 
vessels relax into dilatation. If these observations be correct, chloroform first 
stimulates and afterwards depresses the vaso-motor centres. Confirming this are 
the important experiments of Gaskell and Shore, who find that the local application 
of chloroform to the medulla or its injection into the cerebral artery produces an 
immediate rise of blood-pressure, usually accompanied by a slowing of the heart, 
which is followed by a fall of pressure so soon as the chloroform is able to diffuse 
itself throughout the circulation. Gaskell and Shore further so connected the 



♦Glover (Edinb. Med. Journ., 1842), Gosselin (Arch. Gin., 1848), Anstie. and H. C. Wood. 



ANKSTIIKTICS 33 

oarotid arteries and jugular vein of an animal (A) with the similar vessels of a 

Second animal (15) that the brain of A was fed exclusively with blood from B. It 
is plain thai chloroform given to 15 would reach (he brain of A but would not, reach 
the heart of A. Under these circumstances it was found that chloroform adminis- 
tered to 15 produces rise of blood-pressure in A. In a second series of experiments 
the blood-vessels of A were so connected with those of 15 that when chloroform 
was administered to B it reached the heart of A and all other portions of the body 
except the brain. When this was the case, chloroform given to B produced an 
immediate fall of pressure in A without there having been any rise. In other words, 
when chloroform reached the vaso-motor centres and not the heart, it caused rise 
of arterial pressure; when it reached the heart and not the vaso-motor centres, 
it caused fall of pressure. In accord with the results of Gaskell and Shore, it has 
been found by Embley that the local application of chloroform to the vaso-motor 
centres produces rise of the arterial pressure, which is presumably due to stimu- 
lation of the vaso-motor centres. In common with other observers, Embley found 
that later in the chloroformization there is a vascular paralysis which he believes 
to be due to a direct action of the chloroform on the muscles of the vessels. 

Respiration. — So soon as psychical excitement has passed off, or, 
at first, if there be no such excitement, the respirations may be 
rendered slower by chloroform, but after a time they are generally 
quickened, and as the inhalation is persisted in they become more 
and more shallow, irregular, and distant, and finally cease. In 1870 
Paul Bert asserted that during chloroformization there is more than 
the normal percentage of oxygen in the blood, but in 1885 he affirmed 
that there was less than the normal percentage. There does not seem 
to be much doubt that the results of L. G. de Saint-Martin are correct, 
— namely, that while (probably on account of excessive respiration 
from excitement) in the beginning of chloroformization there is 
sometimes hyperoxygenation of the blood, the rule during full anes- 
thesia is decrease of the oxygen of the blood with increase of the 
carbonic acid. 

• Blood. — As was first demonstrated by Harley, five per cent, of 
chloroform in the blood destroys the red corpuscle with a final 
deposition of crystals of oxyhemoglobin. 

Boettcher was, we believe, the first to study these changes closely. The first 
alteration noticeable in the red blood-disks is a diminution of their size, which A. 
Schmidt and F. Schweiger-Seidel assert to be due to contraction, because when 
blood is treated with water until the red globules disappear, and carbonic acid gas 
is passed through the liquid until they reappear, on the addition of chloroform the 
sharply contoured bodies will be seen to undergo marked contraction. As was 
first shown by Boettcher and confirmed by Schmidt and Schweiger-Seidel, chloro- 
form alone produces no other alteration than contraction in the red blood-disks; 
if, however, air be admitted to blood containing chloroform, the corpuscles rapidly 
disappear, dissolving in the serum, out of which, after a time, oxyhemoglobin crys- 
tallizes. Both of the authorities quoted believe that the latter changes are due to 
oxidation. Boettcher states that chloroform-vapor mixed with air converts enough 
of the oxygen of the latter into ozone to react with iodized starch-paper; and 
Schmidt and Schweiger-Seidel have found that an excess of carbonic acid in the 
blood interferes with the changes caused by chloroform. The facts just noted indi- 
cate that the blood changes are the result of simple oxidation, but the studies of F. 
Kriiger show that chloroform, at least outside of the body, produces a series of 
chemical changes in the hemoglobin. 
3 



34 GENERAL REMEDIES 

How far, during ordinary narcosis, chloroform causes changes in 
the blood is uncertain. A very sensitive test of the destruction of 
the red disks in the body is found in the production of icterus; icterus 
follomng chlorofonnization is very rare, but the assertion of Frerichs 
thai it does occur is correct. 

Bernstein and Leyden have found traces of bile-pigment in the human urine 
after chloroform-narcoeiB; while Nothnagel detected bile coloring-matter in the 
urine of rabbits after .subcutaneous injection of chloroform or ether. Husemann 
intimates, on what authority we do not know, that after anesthesia bile-acids (the 
precursors of icterus) appear in the urine; but Kappeler, in twenty-five cases of 
chloroform-narcosis, was not able to obtain a trace of biliary coloring-matter. 
Sokolovski asserts that the first few hours after chloroformization there is a de- 
crease of the immature white blood-corpuscles, with an increase of the mature white 
blood-corpuscles, followed by gradual return to normal. 

General Nutrition. — That chloroform affects the general nutrition 
of the body is demonstrated by the wide-spread fatty degeneration 
which sometimes follows long-continued narcosis produced by it 
(see page 50), as well as by the observations of Strassmann, who 
found that a pronounced increase of the nitrogenous elimination 
follows chloroform-narcosis, an increase which would seem to be 
directly due to the anesthetic, since Salkowski demonstrated that 
chloroform-water given to dogs distinctly increases the destruction 
of nitrogenous substances in the body without producing narcosis. 

Therapeutics. — For a discussion of the use of chloroform as an 
anesthetic, see Practical Anesthesia, p. 37. 

When administered by the mouth in sufficient quantity, chloro- 
form produces symptoms similar to, but much more permanent than, 
those which it causes when inhaled. It is, however, very rarely, if 
ever, used in this way for its constitutional effect, but is sometimes of 
advantage in severe neuralgia. When for any reason quinine cannot 
be administered in an ague, a sufficient dose of chloroform (one-half 
to one fiuidounce) to produce a mild narcosis, just before the expected 
time for the recurrence of the chill, will often abort it. Chloroform 
by the mouth has been also highly recommended as a vermifuge in 
cases of tapeworm, but is of doubtful value. 

When chloroform is taken into the stomach, a considerable portion 
of it is, without doubt, evaporated, so that the intestinal canal becomes 
filled with the vapor. Chloroform, therefore, when so placed, exerts 
both a local anodyne and a stimulant carminative action. For this 
reason it is valuable in ordinary colic and in colica pictonum. 

Externally, as a rubefacient and anodyne, chloroform is very 
largely combined with other substances into liniments, which are 
especially useful in cases of chronic neuralgic or rheumatic pains. 

The deep injection of half a drachm of chloroform has been recom- 
mended very strenuously by Bartholow in obstinate neuralgia, and 
has found some favor in France. In the only case in which we have 
tried it, one of trigeminal neuralgia, the local symptoms caused by it 
were so severe as to imperil the life of the patient. 



ANESTHETICS 35 

Toxicology. — Poisoning has been produced by the swallowing 
of chloroform. The symptoms induced have been stupor, with 
contracted, or, in later stages, dilated pupils, and a stertorous respira- 
tion, which finally becomes very irregular, shallow, and often distant. 
The amount necessary to destroy life probably varies greatly, but, 
according to L. Lewin, a single fluidrachm has produced death. 
In some cases* the fatal result has occurred from secondary gastritis 
many days after taking the medicine; and not rarely violent gastritis 
with jaundice apparently from inflammation of the gall-ducts has 
been produced. Recovery has occurred after the ingestion of three 
fiuidounces without vomiting;! also five fluidounces. After the 
evacuation of the stomach, by the stomach-pump, the treatment 
should be similar to that employed to combat the accidents of chloro- 
form anesthesia (see p. 46). Death may occur during the narcosis, 
or the patient may survive this and perish from inflammation of the 
trachea, oesophagus, and stomach, caused by the local action of the 
chloroform. 

The recognition of chloroform as the probable cause of any given 
death cannot be based upon the post-mortem appearances. Indeed, 
the latter are of no value in deciding such a question. The anesthetic 
may, however, be recovered by distillation of the lungs and blood 
within a certain period of time after death. As to the length of this 
time, so far as we are aware, no investigations have been made. 

Criminal Relations. — Experiments made at the Philadelphia 
Hospital and confirmed by Dolbeau and by Paugh have proved that 
persons sound asleep may be chloroformed without being awakened. 
Anesthesia cannot, however, be produced in any one partially awake, 
or even sleeping lightly, without his or her knowledge. 

Quite a number of professional men have been accused, and some 
convicted on the charge, of committing rape on females in whom they 
had induced anesthesia. No doubt the women believed that they had 
been violated; but it is certain that in many of the cases they mistook 
for the real act the subjective erotic sensations induced by the chloro- 
form or ether. The valuelessness of the testimony of persons as to 
occurrences during the time of their intoxication with anesthetics 
should be recognized in law as a governing principle of evidence. 

ETHYL CHLORIDE. 

Ethyl Chloride (dtthylis Chloridum) (C 2 H 5 C1) is a colorless, 
extremely volatile liquid of specific gravity (at 0° C.) of 0.918, 
boiling at 12.5° C. On account of its volatility, it has been much 
used under various names to produce local anesthesia by freezing. 
Recently ethyl chloride has been employed as a general anesthetic. 
It acts very rapidly and recovery occurs abruptly on removal of 
the drug. It was partially studied physiologically in 1892 by Wood 

* N. Y. M. R., July 11, 1885. 
t B. M. J., 1882, ii. 776. 



36 GENERAL REMEDIES 

and Cerna, who found thai it produced an amount of circulatory 
depression disproportionate to its anesthetic properties. In Le- 
bet's experiments upon rabbits, the intravenous injection was found 
to produce great circulatory depression. Embley finds that the 
action of el byl chloride is very similar to that of chloroform, being a 
marked depressant to the heart muscle and also somewhat relaxant 
in its effects upon the arterioles. Moreover, Malherbe and Rou- 
binovitch have proven with Rotain's sphygmomanometer that in 
man the arterial tension is almost always clearly lessened. 

In 1902, Lotheisen reckoned the mortality from ethyl chloride as 
1 in 16,000. McCardie collected 9700 cases in England, with 4 deaths. 
It would appear, therefore, that ethyl chloride is about as dangerous 
as an anesthetic as chloroform. 

For prolonged operations the extreme fugaciousness of its action 
makes it less desirable than ether and chloroform; and for short 
operations nitrous oxide is so infinitely safer that the use of ethyl 
chloride as a general anesthetic seems hardly justifiable. 

Ethyl Bromide is a colorless, very volatile, mobile liquid, 
having the specific gravity 1.49, of a sweet, chloroform-like smell; 
not readily inflammable. Any preparation of it which has color, or 
seems irritating, or has a disagreeable smell, is unfit for medicinal use. 
It must clearly be separated by the practitioner from ethylene bromide, 
which has a specific gravity 2.16, and solidifies at 32° F. into a crystal- 
line mass. Scherbatscheff has collected four deaths produced by the 
substitution of ethylene bromide for ethyl bromide. Ethyl bromide 
degenerates under the influence of light and air, and should, therefore, 
always be kept in small bottles of dark glass, closely corked. 

Proposed as an anesthetic in 1849, exploited by Rabuteau in 
France and by L. Turnbull in the United States in 1876-77, ethyl 
bromide has been used to a considerable extent as an anesthetic on 
account of the rapidity of its effects. It has, however, in recent 
years been almost totally abandoned in favor of ethyl chloride. Its 
influence usually manifests itself in a few seconds and lasts not longer 
than three minutes after the removal of the inhaler. 

The physiological action of ethyl bromide has been partially 
studied by Schneider, Thornton and Maxwell, Abonyi, H. C. Wood, 
Ginsburg, and S. W. Cole with results apparently not altogether 
concordant.* 

All observers agree that in the narcosis the arterial pressure finally 
falls, but Ginsburg and Schneider note that this fall is preceded by a 
rise in the arterial pressure, which appears not to have been present 
in the experiments of Thornton and Maxwell or of H. C. Wood. The 
recent work of Tcherbacheff, who found that ethyl bromide causes 
death from cardiac paralysis with or without pulmonary cedema, 

* We are not aware that the purity of the ethyl bromide used has been proved by any of 
the experimenters. Linguistic difficulties in regard to the Slavonic papers have compelled us to 
rely upon abstracts. 



ANESTHETICS 37 

accords with the early conclusions of H. C. Wood — that ethyl bromide 
acts upon the heart in a manner similar to chloroform. 

The respiratory action of ethyl bromide has not been carefully 
studied. It probably is a centric depressant. Livon finds, from analy- 
sis of the gases of the blood, that during the anesthesia produced by 
the ethyl bromide there is lessening of the carbonic acid with aug- 
mentation of the oxygen. According to Brinton it differs essentially 
from the other anesthetics in that there is no muscular relaxation 
during the narcosis. 

In the absence of conclusive statistics, ethyl bromide appears to 
be at least as immediately dangerous as chloroform, and distinctly 
more so in its secondary results. It is true that Gilles claims that with 
a commercially pure bromide twenty thousand successive adminis- 
trations of ethyl bromide in Germany had been without death, and 
that the fatal results have been due to impurity in the drug. This 
certainly does not apply to the deaths recorded by A. Gleich and 
Suarez de Mendoza. 

Pental — Trimethylethylene. — This is a colorless, highly inflammable 
liquid, boiling at 100° F., originally proposed by W. Lombardino as a practical 
anesthetic. It acts with great promptness without marked disagreeable symptoms, 
producing a short narcosis, which is, however, longer than that caused by ethyl 
bromide. In three hundred narcoses by it, P. Philipp failed to find any depression 
of the heart or severe asphyxia. Pental is also commended by Kleindienst, who, 
however, noted that very frequently three or four days after the narcosis there was 
abundant albuminuria, and not rarely hematuria or hemoglobinuria occurs. In a 
study of the drug by David Cerna, anesthesia caused by it in the dog was found to 
be accompanied always by marked fall of the arterial pressure, and the conclusion 
was reached that the remedy depresses the heart. The alleged action of pental 
upon the kidneys, if it be true, negatives its use as a practical anesthetic. From 
the statistics of Gurlt, it is the most dangerous of all the anesthetics, there having 
been three deaths in the six hundred reported narcoses. 

PRACTICAL ANESTHESIA. 

Choice of Anesthetic. — Although various substances have from 
time to time been used as anesthetics,* the surgical profession has 
practically settled down to the employment of either ether or chloro- 
form, and experience seems to show that there are no other known 
agents which act as well as do these two liquids. The question 
as to which of them should be preferred is a vital one, as are also the 
questions how to recognize and how to treat the accidents which 
occur during anesthesia. It must be, in the beginning, granted that 
the production of anesthesia is always attended by a danger which, 
though small, is positive, and that fatal accidents will always occur 
from time to time. There are few things in medical literature more 
tiresome than the arrogant assertions of various surgeons that they 
have never had a fatal accident from chloroform or ether because of 

* From time to time various surgeons have essayed to assist in the production and prolonga- 
tion of anesthesia by the use of narcotic alkaloids. Hypodermic injections of morphine given half 
an hour before the inhalation of the drug have been much employed, but it is doubtful whether 
they are of real advantage. In 1900, Schneiderlin proposed the substitution of scopolamine-mor- 
phine narcosis for ordinary surgical anesthesia and his method has found some following (see p. 111). 



38 GENERAL REMEDIES 

the special methods by which they have used them. May their conceit 
die with them. All that a surgeon can hope for is to reduce the number 
of these accidents to a minimum. 

Chloroform has the advantages over ether,— that it produces 
anesthesia much more quickly, that it is less unpleasant to the patient, 
usually does not cause so much struggling and is less likely to be fol- 
lowed by after-nausea and vomiting. These advantages, while not 
to be lightly thrust aside, are not to be compared in importance with 
the question of the comparative danger of the two anesthetics. We 
may reach a conclusion as to this factor either by studying the 
statistics, or by a study of the physiological action of the two drugs. 

For reasons given by H. C. Wood, in his address before the Berlin 
International Congress, it is doubtful whether one-half of the deaths 
produced by anesthetics have been reported, though many have been 
recorded. The consensus of the studies of Coates, Gould, Garree, 
and Gurlt, covering in all several millions of inhalations, places the 
mortality from chloroform at about one death in about 3,500 cases; 
from ether, at about one in 15,000. It must be considered established, 
therefore, that the ratio of deaths from chloroform* is about four 
times greater than from ether. 

The study of the physiological effects of the drug must likewise 
lead to the conviction that chloroform is much more dangerous than 
ether. Chloroform is, at least, as active a respiratory poison as ether 
and, besides, is a direct depressant to the heart, while the effects of 
ether upon that organ are comparatively slight. This opinion has 
been controverted by some, especially by the so-called Hyderabad 
Commission, but it seems unnecessary to-day to go into the details 
of the proof of this truth. The evidence brought out by H. C. Wood 
shows that — "chloroform acts much more promptly and much more 
powerfully than does ether, both upon the respiratory centres and 
the heart; that the action of chloroform is much more persistent and 
permanent than is that of ether; that chloroform is capable of causing 
death either by primarily arresting the respiration or by primarily 
stopping the heart, but that commonly both respiratory and cardiac 
functions are abolished at or about the same time ; that ether usually 
acts very much more powerfully upon the respiration than upon the 
circulation, but that occasionally, and especially when the heart is 
feeble, ether is capable of acting as a cardiac paralyzant and may 
produce death by cardiac arrest at a time when the respirations are 
fully maintained." These conclusions have been confirmed by John 
A. Mac William, who has recorded cases of death in the lower animals 
from chloroform, in which there was primary collapse of the heart; 
and by the studies of the Lancet Commission, which found that out 
of three hundred and fifty-seven deaths caused by chloroform, whose 

* It is probable that chloroform is less dangerous in tropical thar /n temperate climates. 
Evans presents evidence in confirmation of this to show that deaths from chloroform are more 
frequent during the cold seasons of the year. It is entirely possible that the increased volatility 
of this drug, at higher temperatures, facilitates its elimination from the body and therefore lessens 
the dangers of its use. 



ANESTHETICS 39 

records it had examined, the fatal result was caused by cardiac failure 
two hundred and twenty-seven times, by respiratory failure eighty 
limes, and by simultaneous failure of the two functions seventy- 
seven times. 

On account of its danger we are firmly convinced that, under 
ordinary circumstances, ether should always be given the preference 
over chloroform in the production of general anesthesia. There are 
certain conditions, however, in which a careful surgeon is justified 
in his choice of chloroform. 

Because of its far greater potency in proportion to bulk, in cases 
where the anesthetic has to be transported, as in military surgery, 
the impracticability of carrying the large quantities of ether necessary, 
affords justification for the use of chloroform. Further, in cases where 
rapidity of action is essential, as in strychnine-poisoning or under 
certain exigencies in military surgery, chloroform is again to be 
employed. 

Besides these conditions, however, there are certain diseases which 
greatly enhance the danger of ether, and may properly lead to a 
preference of chloroform. Foremost among these stand inflammations 
of the respiratory tract. On account of the concentration of ether 
vapors, necessary to produce anesthesia, there is generally much more 
irritation of the respiratory mucous membranes, which may give 
rise to a dangerous or even fatal pulmonary inflammation.* 

Disease of the kidneys is frequently spoken of as an indication 
for a preference of chloroform. This opinion, however, is not well 
borne out by either scientific considerations nor yet by the practical 
results which have followed the use of the anesthetics. 

Albuminuria may be considered a sufficiently accurate evidence of renal irri- 
tation to enable the practitioner to use it as a working test. A large number of 
studies as to the effect of anesthetics upon the urine have been made by different 
clinicians. Eisendrath states that albuminuria was produced in his cases, — 25 per 
cent, by ether, 32 per cent, by chloroform; and casts were found in 28.3 per cent. 
after ether, 21.4 per cent, after chloroform. In Wunderlich's studies the results were 
24.6 per cent, after ether, 34.8 per cent, after chloroform. f Ogden found tube-casts 
in 70 per cent, of etherizations. Statements of other investigators, whom we shall 

* Ether Pneumonia. — Severe and even fatal pneumonia has so frequently followed the use of 
anesthetics that the possibility of its occurrence must be considered one of the serious dangers of 
anesthesia. Allowing that particles of food may enter the lungs during the narcosis and produce 
inflammatory changes, there has been a tendency to believe that ether pneumonia more frequently 
follows the use of ether than of chloroform, and is due to the local irritant action of the ether. 
The research of Richard Holscher has led him to the conclusion that the pneumonia is really due to 
the inhalation of bacteria from the mouth into the lung, that during etherization there is prac- 
tically no irritation of the bronchial mucous membranes by ether, and that the rales which are 
heard during the narcosis are due to the inhalation of saliva which may largely be avoided by lowering 
the head, turning it to one side, and keeping the mouth as free as possible from the secretion. Any 
mechanical obstacle to breathing, according to Holscher greatly increases the likelihood of the 
inspiration of saliva, and the consequent danger of pneumonia. According to our belief, this 
research, although extremely important and suggestive as pointing out one cause of ether pneu- 
monia, does not disprove the deleterious effect of the irritant action of ether. 

t For elaborate articles on the action of chloroform on the urine and kidneys, see F. Nachod 
(Archiv f. Klin. Chirurgie, 1890, li.), also Offergeld. Babacci and Bebi {II Polyclinico, 1896, iii.) 
reach the conclusion that, although ether produces slight changes in the kidneys more frequently 
than does chloroform, it never causes such profound alteration. 

As bearing upon the question of the effect of ether anesthesia upon the kidney, it is interesting 
to state that F. S. Watson and W. T. Bailey have found that in the normal kidney, so far as the 
so-called Phloridzin Test is concerned, ether increases functional activity of the kidney, but when 
the kidney is already diseased seems from the beginning to depress the renal function {Med. and 
Surg. Rep., Boston City Hospital, 1902). 



40 GENERAL REMEDIES 

not quote in detail, indicate that the occurrence of distinct albuminuria after anes- 
thesia in jmt^oii^ with sound kidneys is less frequent than these statistics would 
indicate; bul all the statistics strongly point towards the opinion that, while both 
ether and chloroform seriously affect the kidneys, ether is less dangerous than is 
chloroform. These clinical conclusions arc certainly borne out by the results ob- 
tained in animals by various investigators. According to Kemp and Thompson, 
during etherization in the animal there is always accompanying the first rise of blood- 
pressure an expansion of the kidney followed by a shrinkage of the organ, if the 
anesthesia be prolonged; but this has been found by Buxton and Levy not to be a 
constant phenomenon. Buxton and Levy failed to produce complete suppression 
with ether, but did get lessening of the secretion and as the result of their research 
think that there is very little evidence to show that ether has an active, direct 
influence upon the secreting structure of the kidney. All observers seem to find 
that in chloroformization the volume and activity of the kidney steadily decrease. 

The choice of the surgeon between the two great anesthetics 
should, in most cases of renal disease, be influenced by the existence 
of secondary effects of the disease. If, for instance, in any case there 
were pronounced degeneration of the heart-muscles, the selection 
should fall upon ether. If there were any reason, on the other hand, 
to believe that there was in the case a tendency to serous exudation, 
the danger of the production of cedema of the lungs by ether through 
its local irritant action would be sufficient reason for the selection of 
chloroform. In doubtful cases of cardiac complication it might be 
good practice to commence the anesthesia with ether, and, when 
once its stimulating action was established, to continue the narcosis 
by the use of chloroform. 

Examination of the Patient. — Before administering the anes- 
thetic, careful examination should be made by the anesthetizer for 
the determination of any physical condition which would enhance 
the danger of the anesthesia. Among these conditions most commonly 
to be looked for are: Organic Brain Diseases, including Tumors; 
Atheromatous Conditions of the Blood- Vessels; Organic Affections of 
the Heart, of the Lungs, and of the Kidneys. 

Brain. — Brain-tumors and other organic forms of cerebral disease 
are very serious contraindications to the use of anesthetics; even 
where there is no demonstrable brain-lesion, if there be reason strongly 
to suspect atheroma of the vessels, anesthesia should be induced with 
the greatest reluctance. In a number of cases apoplexy has resulted 
during or immediately after the anesthesia. Moreover, death has 
frequently abruptly occurred immediately after the sudden removal 
of a large cerebral tumor — the introduction of the finger between the 
lobes of the brain— or other procedure which affects the intracranial 
pressure. These deaths have resulted both from respiratory failure 
and from sudden cardiac arrest, and are probably the result of the 
loss of the resisting power of the respiratory and vaso-motor centres, 
making them unable to withstand variations of brain-pressure which 
in their normal condition would not seriously influence them. It is 
evident that the surgeon should be as careful as possible in his opera- 
tive procedures to avoid sudden disturbances of the brain. Which 
anesthetic is to be given the choice, in diseases of the brain, there is 



ANESTHETICS 41 

not yet sufficient evidence to clearly indicate. There has been in 
some, to a certain extent, a feeling, not supported by any positive 
evidence, that chloroform is preferable, but in a discussion which 
took place in the College of Physicians of Philadelphia, November, 
1902, a number of cerebral surgeons of large experience were unani- 
mous in asserting that, in cerebral surgery, ether is the least dangerous 
anesthetic. 

Heart. — When valvular disease of the heart does not produce any 
distinct functional disarrangement of the heart, and when the heart- 
muscle is in a fair condition of health, anesthesia may be induced, 
provided the circumstances of the case are such as to justify the 
surgeon taking a slightly increased risk. The key to the situation is 
not the valvular lesion, but the condition of the muscle. A loud 
murmur usually depends for its loudness not only upon the character 
of the valvular lesion but also upon the force which drives the blood 
through the diseased orifice. A loud murmur is, therefore, on the 
whole, not more strongly contraindicative of anesthesia than is a 
feeble one; indeed, as the feeble murmur is more commonly asso- 
ciated with feeble heart-walls, greater care must be exercised when 
such murmur exists than when a loud bruit everywhere forces 
itself upon the physician's attention. In all cases of heart disease, 
whenever it is possible to avoid the use of an anesthetic by the em- 
ployment of cocaine or by other local device, this should be done. 
No condition of the heart is, however, an absolute contraindication 
to the use of the anesthetic; under certain circumstances anesthesia 
may be produced when the heart is in advanced fatty degeneration. 
It must be remembered that the shock and nerve-strain which attend 
a major surgical operation without anesthesia would endanger the 
arrest of a fatty heart even to a greater degree than would the anes- 
thesia, so that the question is, after all, as to the imperativeness of 
the proposed operation. 

In diseases of the heart the action of chloroform upon the heart 
makes it very dangerous. In cases with wide-spread pulmonic engorge- 
ment, and a tendency to exudation into the lung- vessels and smaller 
bronchial tubes, the local irritant action of ether upon the mucous 
membranes is so deleterious that the surgeon is placed, as it were, 
between Scylla and Charybdis, and may in an individual case have 
great difficulty in deciding what is best. Some surgeons prefer 
under these circumstances the so-called A. C. E. Mixture, which 
contains too much chloroform to be of any advantage. A better 
mixture consists of six parts of ether and one of chloroform, added 
together at the time of use. Chloroform is especially dangerous 
when orthopncea exists; it is doubtful whether in such a case its use 
is ever justifiable. 

Lungs. — Organic disease of the lungs seems to be a less serious 
bar to the use of anesthetics than might naturally be expected. The 
danger appears to be in proportion to the acuteness of the disease 
rather than to its extent. A chronic pulmonary condition, such as 



42 GENERAL REMEDIES 

tuberculosis, may involve a considerable proportion of the pulmonary 
area without forbidding the use of the anesthetic, while in ordinary 
acute bronchitis the anesthesia may be attended with grave risk. 
Only under the most urgent circumstances should anesthesia be 
attempted when in an acute pulmonary disease the symptoms are 
of sufficient intensity to produce even slight dyspnoea. In recent 
pleurisy or pleuro-pneumonia, with any embarrassment of the respi- 
ration or duskiness of the countenance anesthetization is almost 
absolutely unwarrantable. 

Of the chronic pulmonic affections, probably emphysema, asso- 
ciated as it so frequently is with weakness of the right heart, causes 
the most solicitude to the anesthetizer. The irritant local action of 
ether is an important element when the lining membrane of the tubes 
or air-vessels is seriously implicated; indeed, our own opinion is 
very positive that in some of the deaths which have occurred in persons 
with diseased kidneys from cedema of the lungs directly after etheriza- 
tion the cause of death has been the local irritant action of the ether. 
It would appear also that wide-spread organic changes in the lungs 
sometimes so interfere with the absorption of ether that it becomes 
exceedingly difficult to produce complete anesthesia. The dictum of 
Hewitt, that in extreme emphysema, in chronic bronchitis attended 
by expectoration and dyspncea, and in advanced pulmonary phthisis, 
chloroform or some other mixture containing chloroform should be 
employed, is, we believe, correct. 

In obstructive laryngeal disease, or when contraction of the lumen 
of the trachea, either from within or without, produces dyspncea, 
extreme caution must be exercised in the use of the anesthetic. Under 
these circumstances the chances of ether increasing the mechanical 
asphyxia by irritating the larynx or trachea are very great, so that 
chloroform is preferable; or chloroform may be employed at first, 
and ether given when the reflexes have been abolished by the obtund- 
ing of the nerve-centres. When the laryngeal obstruction is of the 
nature of a spasm and not of an organic change, the use of the anes- 
thetic is free from extraordinary danger; but it must be remembered 
that frequently in such cases there is more or less laryngeal irritation, 
so that chloroform is preferable to ether, — a conclusion which is 
strengthened by the necessity which often exists for the prompt 
action of the anesthetic. 

In certain cases the mechanical obstruction may be a tumor in the 
mouth or other lesion above the respiratory tract proper, but if the 
respiration be interfered with, the general principles just enunciated 
hold good. 

Hepatic Conditions. — L. G. Guthrie has called attention to the 
excessive fatality attending the use of chloroform in children suffering 
from fatty degeneration of the liver. The time of death in nine recorded 
cases was from ten hours to nine days after the operation, so that the 
cases really belong among those considered in the After-effects of 
Anesthesia (see page 49). There is sufficient ground for the generali- 



ANESTHETICS 43 

zation that anesthesia should be produced with the greatest reluctance 

in all persons suffering from chronic fatty degeneration of the liver, 
and that when anesthesia must he produced in such cases, ether and 
not chloroform should always be selected. 

Diseases of the Kidney. — So far as our reading goes, Thomas A. 
Emmet was the first to report cases of fatal urinary suppression 
produced by the inhalation of ether in persons suffering from chronic 
Bright's disease. His statements have been followed by reports of 
numerous similar cases, and led to the wide-spread opinion that 
ether should not be used when there was chronic disease of the kidneys. 
It is now, however, established that chloroform is capable of causing 
severe renal irritation, and the whole drift of the evidence is to show 
that in this respect it is much more active than is ether, so that, 
though renal disease is a contraindication to the use of any anes- 
thetic, if anesthesia must be pro- 
duced under the circumstances, 
ether is safer than is chloroform. 
(See p. 39.) 

In regard to the preparation of 
the patient aside from his physical 
examination, the rules are very 
simple, but very important. 

First, except in emergency oper- 
ations, the anesthetic should not 
be given less than six hours after 
a meal; second, clothing should 
always be loose, so as to not 

obstruct in any way respiratory FlG _ 2 ._ Allis Ether Inhaler . 

movements; third, false-teeth, and 

other movable objects should be taken out of the mouth; finally, 
the anesthesia should always be commenced in a recumbent posture. 

Administration of the Anesthetic. — The question of the inhaler 
to be used is one of some importance. Although not able to give 
definite statistics upon the fact, we are strongly inclined to believe 
that deaths from anesthesia, and especially from ether, are propor- 
tionately more frequent in Europe than in America. If this be so, 
one reason, it seems to us, is to be looked for in the use of the Clover 
and other forms of closed inhalers, with which the anesthesia pro- 
duced is to a greater or less extent due to mechanical asphyxiation. 
Sherrington and Sowton have shown that the presence of carbonic 
acid in the perfusing liquid, exaggerates the depressant action of 
chloroform upon the heart. 

For the inhalation of ether the inhaler invented by O. H. Allis 
is probably as good as any upon the market. It is based upon the 
theory that the patient to be etherized should be supplied with an 
abundance of air impregnated with the vapor of ether. It consists 
essentially of a series of foldings of muslin on a wire framework, 
arranged almost like the gills of a fish, so as to allow the air to pass 




44 GENERAL REMEDIES 

freely through, but everywhere to come in contact with the ether. 
The ether is dropped or sprinkled equally over the whole surface of 
the muslin, whence it is rapidly evaporated so that the patient can 
receive as large a dose as desirable of the anesthetic j^et the respiration 
be not in the leasl interfered with. For chloroform, preference may 
be given to Esmarch's inhaler or one of its various modifications. This 
consists of a light wire framework over which is fastened surgical 
gauze, the framework being so arranged that the gauze is held some 
distance from the patient, avoiding the danger of inhaling the con- 
centrated chloroform vapors. An inhaler which has received con- 
siderable commendation in Europe is the Roth-Drager inhaler, an 
apparatus invented for the purpose of giving a mixture of chloroform 
with oxygen. It is claimed by Roth that under these circumstances 
the chloroform remains unchanged, although Ernst Falk believed that 
his chemical studies have demonstrated that after twenty minutes 
of narcosis there is a distinct decomposition of the chloroform. Either 
ether or chloroform, however, may be safely and confidently admin- 
istered without the use of any more complicated mechanism that a 
few thicknesses of surgical gauze. Four or five thicknesses of gauze 
may be lightly held over the mouth and nose of the patient and 
the ether dropped, drop by drop, upon the gauze just below the 
nostrils. When chloroform is the anesthetic the gauze should be 
held a little distance from the face to allow the admixture of air 
beneath the gauze. 

The unpleasant sensation which gives the patient so much dis- 
comfort may be largely avoided if not altogether obviated by a very 
slow administration, beginning with one or two drops at a time and 
increasing gradually as the patient becomes accustomed to the 
anesthetic until the appearance of delirium of the first stage, when, 
if ether is being used, it should be pushed as rapidly as possible. It 
must be remembered that the danger from ether is largely proportion- 
ate to the total quantity of the anesthetic, while the danger from 
chloroform is chiefly dependent upon the concentration of the chloro- 
form vapor in the air at a given moment. Never more than three 
and one-half per cent, of the chloroform should be contained in the 
inspired air.* 

The use of ether at night requires care. We have seen a flame, by 
lighting the vapor, pass over eight feet and set on fire the ether sponge 
and the patient. Since the vapor of ether is heavier than air, when the 
anesthetic is used at night the light should always be elevated. The 
administration of chloroform at night is also not free from danger. 
Attention has been called by various practitioners to violent catarrhal 
inflammations of the respiratory passages, and even to fatal pneu- 
monias, which have been produced by the use of chloroform in confined 
rooms with artificial light. It has been shown by the analyses of 
Bosshard and others that, under the circumstances mentioned, by 

* For methods of determining the percentage of chloroform in a mixture of its vapor with 
air, see Brit. Mai. J„urn., 1903, vol. i. p. 1420. 



ANESTHETICS 45 

the decomposition of chloroform (hero is liberated free chlorine and 
also phosgene gas, to which probably arc duo the local inflammations.* 

Symptoms.— The narcosis produced by ether and chloroform 
may be, for convenience, divided into three stages: First, excite- 
ment; second, anesthesia; third, collapse. 

The first stage is usually more marked with ether than with 
chloroform. The first symptoms observed are a sense of choking which 
is referable to the irritant action of the vapor upon the mucous mem- 
branes of the upper respiratory tract. This irritation of the fauces 
may lead to great irregularity or even to complete cessation of the 
respiration. 

The respiratory phenomena seem to be the same in the lower mammalia as in 
man. The primary arrest of respiration during the first stages of etherization is 
undoubtedly due to a local irritation of the mucous membranes of the air-passages. 
According to Kratschmer, in the rabbit it is prevented by previous section of the 
trigeminal nerves, but not by division of the vagi; nor does it occur when the ether 
is administered through a tracheal fistula. This would indicate that the respiratory 
disturbance is due to irritation of the peripheral trigeminal nerves, but H. A. Hare 
has found that in the dog tracheal irritation with ether produces respiratory arrest, 
which is, however, prevented by previous section of the vagus. As stated by 
P. Knoll, the arrest of respiration is sometimes replaced by very irregular breath- 
ing. The importance of the matter is increased by the fact that Kratschmer has 
noticed that the disturbances of respiration are accompanied by spasm of the glottis. 
It is evident that these disturbances are reflexes due to irritation of the trigeminal 
nerves in the upper, and of the pneumogastric filaments in the lower respiratory 
tract. They are especially interesting in connection with the asserted direct or 
indirect effect of ether upon the recurrent laryngeal nerve. 

Partly as a result of the irritation of the respiratory tract, but 
largely on account of the alcohol-like delirium produced, the patient 
struggles more or less violently. As in alcohol, the delirium of ether 
or chloroform is of various characters; some patients weep, others 
laugh; some shout, some pray, some rave, and some become exceed- 
ingly pugnacious. In rare instances the dreams are erotic; and 
cases are on record in which there were distinct evidences of the 
occurrence of a complete venereal orgasm. In this stage the patient 
in most cases may be more or less perfectly aroused. In rare instances 
however, unconsciousness has been retained until complete anesthesia. f 
The face is warm, flushed and moist. The pulse is somewhat more 
rapid than normal, largely on account of the struggling of the patient, 
but of good volume. The pupil may be somewhat dilated but readily 
contracts to light. 

The second stage is that of surgical anesthesia. There is complete 
loss of sensation with unconsciousness, the patient being in a deep 
stupor from which he cannot be aroused. The reflexes are mostly 
abolished although certain ones, the conjunctival and respiratory 
reflexes, may be retained. The muscles are relaxed but keep their 

♦Consult Zweifel (Berl. Klin. Wochensch., 1889), D. R. Patterson {London Practitioner, xlii.), 
and Brandenberg (Corr. Bl. f. Schweizer Aerzle, 1897, xxvii.; Arch. f. Hygiene, 1891, xiii.). 

t Coleman 'Sansora, Chloroform, Philadelphia, 1866) states, that he has extracted his own 
teeth without pain; and Snow relates the anecdote of a child who played with his toys during the 
Operation of lithotomy. 



l,i GENERAL REMEDIES 

normal tone. The pulse is, with ether, usually somewhat more rapid 
than normal and of good volume; when chloroform is the anesthetic, 
it is often much softer than normal. The respirations are slow but 
regular and deep. The face is flushed, the skin is warm and moist. 
The pupil is generally contracted.* 

In the third stage there is profound collapse, with rapid feeble 
pulse, very infrequent and shallow respirations. The face is of a 
peculiar livid pallor the result of combined circulatory and respiratory 
failure. The pupil is dilated and non-irritable. All the reflexes are 
entirely abolished and the muscles lose their tonicity. As a result 
of this" loss of muscle tone we get the stertorous respiration and 
drooping of the corners of the mouth. 

Accidents. — In practical anesthesia it is a matter of the 
gravest importance to recognize the coming on of accidents. The 
danger signals to be looked for are: Dilatation of the pupils, the very 
slow or irregular respirations, stertorous breathing, extreme rapidity 
or feebleness of the pulse, changes in the color or expression of the face. 

Before epitomizing the treatment of the accidents of anesthesia it 
seems proper to discuss in detail certain mechanical measures which 
may be practised with advantage, — namely, Inversion of the Body, 
Cardiac Massage, and Artificial Respiration. 

Inversion of the Body.— In the first edition of the present treatise it was written: 
"Whenever there is any failure of the heart's action, as is nearly always the case, 
the body should be laid at an angle of forty degrees, with the head downward, so 
as to favor the passage of arterialized blood to the brain" (E. L. Holmes). Some 
years after this the method was asserted in France to have just then originated with 
Nelaton. It undoubtedly has value. The body of the animal whose circulation 
lias been paralyzed by chloroform acts in a measure like a tube filled with liquid. 
When the feet are raised above the head there is a marked increase in the blood- 
pressure in the carotid, with decrease in the blood-pressure in the femorals; and 
when, on the other hand, the feet are dropped below the head, the blood-pressure 
fails in the carotid, but rises in the femorals. The respiration is not affected by the 
procedure, but a heart which has entirely ceased will often suddenly resume its 
work when the feet are elevated. Inversion causes the blood which has collected 
in the extremely relaxed abdominal vessels to flow into and distend the right side 
of the heart, and this distention may have sufficient influence to stimulate into 
action a failing organ. 

Cardiac Massage. — In 1889 Prus succeeded in restoring animals to life, after 
cardiac arrest during anesthesia, by rhythmically contracting the bared heart with 
his fingers, and this so-called "cardiac massage" has been employed to a consider- 
able extent by surgeons. W. W. Keen collected twenty-eight recorded cases with 
four successes; since this paper one complete recovery has been reported by Sen- 



* Baudin <I.c Pmgres Med., Sept. 1874) called attention to the pupil as a guide in chloro- 
fonnization, stating that, although at first it is uniformly dilated, afterwards it is uniformly immova- 
bly contracted, and that this is t he period for operating. Sehlager is in accord with Baudin; in 
one hundred and twenty out of one hundred and twenty-two cases observed, the pupil was dilated 
during the stage of excitement, and during complete anesthesia narrowly contracted. He also 
states that if during anesthesia the pupil return to normal, more chloroform is required, but if it 
suddenly dilate, danger is imminent. At present, however, the condition of the pupil cannot be 
considered a safe guide in anesthetization. Dogiel (Reichert's Archiv fiir Anat., 1806) affirms that 
in rabbits, during the stage of excitement, the pupil is contracted, during anesthesia dilated. Schiff 
has strenuously combated the conclusions of Baudin; and in a very careful series of experiments 
on animals \Y. II. Winslow found that the state of the pupil varies greatly in the same stage of 
anesthesia. Thus in complete anesthesia, sometimes the pupil was widely dilated, sometimes 
contracted; ami death sometimes occurred with a dilated, sometimes with a contracted pupil, — 
in l he former case probably being syncopal, in the latter asphyxial (Pliila. Med. Times, vi. 275). 



AXKSTIIKTICS 



47 



cert. Three methods have been used: (1) By compression between the hands, 

one being applied outside the chest, and the other directly upon the heart alter an 
abdominal section, but without, opening the diaphragm. (2) By abdominal section, 
and after opening the diaphragm seizing the heart within the pericardial sac. (3) 



a. 2 



is 

S S 




By resection of the chest wall, incision of the pericardium, and grasping the heart 
with one or both hands. The third of these methods involves a major operation in 
surgery, adding distinctly to the surgical dangers of the patient. Especially when 
the abdomen has already been opened by the surgeon, the first, and even the second 
method is easily practised without very serious surgical results. It is at present 
doubtful whether cardiac massage will ever restore cardiac action when the intra- 



is GENERAL REMEDIES 

venous injection of adrenalin and the practice of forced artificial respiration would 
not succeed, but to the use of these methods that of the simpler form of 
cardiac massage (No. 1), especially in abdominal operations, may well be added. 

Artificial Respiration.— The one measure which we have found in experiments 
upon fatally anesthetized animals to surpass, in practical efficiency, all others 
combined is artificial respiration, by means of which animals may be frequently 
resuscitated after all cardiac and respiratory movements have apparently ceased. 

It is evident that the ordinary methods of practising artificial respiration in 
man are exceedingly imperfect and feeble, and that in the accidents of anesthesia 
so-called forced artificial respiration should be at once employed. The principle 
of forced artificial respiration consists simply of pumping air into the lungs by means 
of a belloWB. There are several forms of apparatus for this purpose to be had, 
nearly all based upon the principle originally brought forward by Fell. 

In using this apparatus, the lungs should be thoroughly but slowly expanded 
by each stroke of the bellows, and a respiratory rate of about sixteen to twenty a 
minute be steadily maintained. It is essential to free the lungs and blood of chloro- 
form as rapidly as possible, by quickly changing the residual air of the lungs; but 
of course due care must be exercised that no force sufficient to rupture air-vesicles 
be employed. When the symptoms are protracted, and the bodily temperature 
falls, the bodily heat must be maintained by external warmth, and the tempera- 
ture of the room, unless the air entering the lungs be artificially heated, should 
not be less than 80° F. 

^'hen no apparatus is at hand mouth to mouth insufflation may be tried. A. E. 
Prince reports a case saved in this way. 

In the light of all our present clinical and experimental knowledge, 
the following rules may be formulated as embodying the treatment of 
the accidents of anesthesia: 

First. — Unless the pulse be beating actively, partially or wholly 
invert the body of the patient. 

Second. — Place the index fingers of each hand upon the corre- 
sponding cornua of the hyoid bone, while the middle fingers rest upon 
the angle of the jaw, and then press forward and upward, the same 
force serving to extend the head upon the neck; if this fail to open 
the glottis, by means of a tenaculum, thrust far back into the base 
of the tongue, draw it forward. 

Third. — Make a momentary effort to stimulate respiration by 
slapping the chest, by douching with cold water, or by the method, 
suggested by Hare, of pouring a little ether on the bared abdomen, 
so as to get the effect of cold. Do not waste time, if respiration has 
failed, in any of these attempts. 

Fourth. — Certain drugs are of great use. For stimulation of the 
respiration strychnine is the most potent agent we have; cocaine is 
useful as an adjunct. For failing circulation digitalis would be a 
most valuable remedy were it not so slow in its action; it should, 
however, be given hypodermically, in the hope that it may act in time 
to be of benefit; probably injected intravenously it would be a very 
valuable remedy, but we know of no clinical records of such use. 
Adrenalin given intravenously is a very quick and powerful circula- 
tory stimulant but should not be used indiscriminately on account of 
the danger of causing pulmonary cedema (see p. 246). In severe 
cases of cardiac failure, however, it is of the utmost service. It 



ANESTHETICS 49 

should be administered intravenously in hot (105° F.) normal saline 
solution;* from twenty to thirty minims of the I : 1000 adrenalin 
solution in half a pint of the saline solution may be slowly injected, 
as much as two draehms of the adrenalin solution in two pints of the 
normal saline may he given in the course of one and a half hours. 
Avoid the use of alcohol, it is capable only of harm. The same is 
probably true of nitroglycerin. 

Owing to the closeness of the relations of alcohol to ether and chloroform, H. 
C. "Wood many years ago taught that the administration of alcohol during anesthesia 
was a doubtful procedure; subsequently, R. Dubois determined that in the alco- 
holized animal much less chloroform is required to kill than in the normal animal. 
Then H. C. Wood experimentally proved that alcohol injected into the vein of a 
dog whose heart is depressed by chloroform, if in sufficient dose to exert any per- 
ceptible influence, always increases the cardiac weakness, or, if in considerable 
dose, immediately paralyzes the visens. Without doubt patients have been killed 
by alcohol given to relieve cardiac failure during anesthesia. Experiments similar 
to those with alcohol just spoken of were made by H. C. Wood: with ammonia, 
which was found usually to have a distinct, although very fugacious, influence upon 
the chloroformed heart; with digitalis, which was found to have a very powerful 
stimulant influence upon the heart and blood-pressure; with amyl nitrite, which 
failed to produce any pronounced influence for good; with caffeine, which seemed 
to have little or no power; and with strychnine, which had some slight influence upon 
the blood-pressure, but an enormous one upon the respiration of the chloroformed 
animal. Thus, a respiration which had practically ceased for ten seconds, sud- 
denly, under the influence of an injection of strychnine, became very quick and full. 
Cocaine was not tried, but studies since made with it upon chloralized dogs indicate 
that it has distinct value, especially when given with the strychnine. At the time 
of the experiments just spoken of adrenalin had not been discovered, but as the 
most powerful known stimulant to the circulation it must be of great possible value 
in the treatment of the cardiac accidents of anesthesia. 

Fifth. — Maintain the temperature of the body by the external 
application of heat. 

In 1848 Dumeril and Demarquay showed that during anesthesia there is a 
reduction of temperature. This has been confirmed by Bouisson and by Sulzynski. 
This fall of temperature may, when narcosis is prolonged, amount to 2° F. Whether 
this fall of temperature be, as asserted by Scheinson, due to a lessened production 
of the bodily heat, or whether, as seems to us more probable, it be the outcome of 
an increased dissipation of bodily heat, is of no practical importance to the surgeon. 
The immediate lesson is, that prolonged severe operations should be done in very 
hot rooms, and that when the bodily heat falls it should be maintained by the 
external use of heat, in some cases even by the employment of a hot-water mattress. 

Sixth. — Practise artificial respiration immediately and very 
actively throughout (forced respiration if the apparatus be at hand), 
even when the heart is primarily affected. It must be remembered 
that the residual air of the lung may retain the vapor of the anes- 
thetic and continue to yield it to the system for a considerable time 
after the cessation of its administration. 

After=Effects of Anesthesia. — Many years ago Liman affirmed that 
at least some of the deaths following operations which have been 

* The restorative cardiac action of hot normal salt solution intravenously administered has 
been demonstrated in a series of experiments upon animals by S. Gomberg. 

4 



50 GENERAL REMEDIES 

attributed to the operative procedure have been due to the chloroform. 
The correctness of this view we have demonstrated by having such 
deaths occur in the lower animals after both chloroform and ether 
when there had been no surgical operation, the animal regaining 
consciousness, but by and by passing into a condition of profound 
asthenia, with loss of all functional power, ending in death. These 
deaths are due to anatomical changes in important organs. 

About a decade since it was shown by linger and by Path, that when, in the 
dog, narcosis is maintained for a length of time by the inhalation of chloroform, 
there is produced a fatty degeneration which is usually most marked in the liver and 
kidneys and in the heart-muscles, but may be pronounced in the spleen, in the gen- 
eral epithelial t issues, and in the voluntary muscles. These researches have been 
confirmed in their general results in numerous experiments upon animals by Strass- 
inaiin, by Ostertag, and by Kast and Mester. Tedeschi, in an elaborate study upon 
guinea-pigs, has found that the first anatomical alteration produced by chloroform 
consists of cloudy swelling which may go on to degeneration, or may subside; and 
that even when a considerable degree of apparent fatty degeneration has occurred 
recovery is possible. He also found that these alterations were most severe in the 
nervous system, which is somewhat contrary to the general opinion. Botscharoff 
and S. Schmidt assert tliat they have demonstrated alteration of the heart-ganglia, 
especially vacuolation of the cells, after prolonged cliloroformization. 

Eugene Fraenkel found in four human subjects, dying after prolonged cliloro- 
formization, wide-spread necrotic degeneration, especially affecting the heart- 
muscles and the epithelium of the kidney, and Carmichael and Beattie, and Stiles 
and Macdonald have reported wide-spread fatty changes in man following chloro- 
form anesthesia. As these observations have been abundantly confirmed (Bandler, 
Ambrosius, and our own laboratory), it must be considered proved that chloroform 
has the power of producing tissue-degeneration, ending in death. 

The possibility of after-effects from the anesthetic should certainly influence 
the choice of surgeons. 

According to Desgrez and Nicloux, chloroformization of the lower animals 
causes a great increase in the amount of carbon monoxide in the blood. As this 
sul stance is produced by the decomposition of chloroform by an alkali, and as 
Desgrez and Nicloux have failed to find that it is increased in the blood by etheriza- 
tion, it probably is produced in the blood by the destruction of the chloroform, which 
destruction must be accompanied by the formation of various chlorine compounds. 

On the other hand, the destruction of ether in the system can scarcely yield 
other than harmless educts, so that, a priori, after-effects are much more probable 
from the use of chloroform than from ether. This probability is strongly confirmed 
both by experimental and clinical evidence. As the result of many years' experience 
in the physiological laboratory, we are very sure that after-deaths are much more 
frequent in animals which have been chloroformed than after ether. 

In experiments performed by William Carter and H. C. Wood in the Univer- 
sity of Pennsylvania changes similar to those caused by chloroform were found 
in the dog after etherization. These studies have been corroborated by the researches 
of Ferdinand Schenck and of Tedeschi. Again, in a woman whose death occurred 
twenty-four hours after a prolonged etherization in the University Hospital, without 
obvious cause, wide-spread tissue-changes were found. Miiller found that chloro- 
form, ether, ethyl chloride, ethyl bromide, and hydrated chloral were all capable 
of producing these changes, but that they were less marked after ether than after 
chloroform. In his experiments it was found that if a second narcosis was produced 
before the repair processes were completed the baneful effects were much intensi- 
fied even if different anesthetics were used. He warns therefore that after a pro- 
longed anesthesia no second narcosis should be undertaken for at least three days. 

In this connection may be mentioned the observations of E. Becker who, in 
two hundred and fifty experiments made with ether, ethyl bromide, and chloro- 



ANESTHETICS 51 

form, found that the anesthesia was followed by pronounced aectonuria, which ho 
believed to be due to increased destruction of albumin. In three diabetics he noticed 
great increase in the amount of acetone in the urine,— an indication that under 
certain circumstances diabetes should be considered a contraindication to the uso 
of an anesthetic. Hrachett, Stone and Low report seven cases of fatal acetonuria 
following ether anesthesia in children suffering with muscular atrophies. 

LOCAL ANESTHESIA. 

Of the drugs which are employed for the production of local 
anesthesia, cocaine still stands pre-eminent, but its common use for 
other purposes has led us to discuss its physiological action and 
therapeutic use fully in the chapter on Delirifacients see p. 117). 

Eucaine. — Under the name of eucaine two allied chemical substances have 
been put upon the market, each depending, according to Vinci, for its anesthetic 
properties upon the presence of a benzoyl molecule in its constitution. These sub- 
stances have been distinguished in commerce by the names of Alpha-Eucaine and 
Beta-Eucaine. Alpha-Eucaine is chemically n-methyl-benzoyltetramethyl-y- 
oxypiperidincarboxylicmethylester; Beta-Eucaine is benzoylvinyldiacetonalka- 
mine. Eucaine of the drug stores is at present beta-eucaine. Beta-eucaine is soluble 
in water to the extent of about three and one-half per cent. The acetate has been 
proposed as more soluble. 

According to Vinci, alpha-eucaine is a depressant to the spinal cord, and Ver 
Eecke has found it to be a direct muscle paralyzant which acts more powerfully 
upon the heart-muscle than upon the voluntary muscle, so that death from cardiac 
diastolic arrest occurs before complete general paralysis. Ver Eecke states that in 
mammals the arterial pressure is markedly affected and the respiration is first 
stimulated and finally paralyzed centrically. The same author failed to find the 
poison in the urine after its administration, and believes that it undergoes destruc- 
tion in the body. He also states that in chronic poisoning with alpha-eucaine there 
is a wide-spread fatty degeneration which is especially marked in the heart-muscle. 

Vinci found that beta-eucaine paralyzes the peripheral motor nerves as well as 
the sensory, does not dilate the pupil, paralyzes the vaso-motor centres, and slows 
the heart even after the vagus has been paralyzed with atropine. 

As a local anesthetic eucaine is somewhat less powerful than cocaine, and does 
not produce primary vaso-motor constriction nor vaso-paralytic after-effects. 
The three- to five-per-cent. solution will rapidly and completely anesthetize the 
cornea without dilating the pupil or paralyzing the pupillary reflexes. It may be 
used in solutions of from 2 to 10 per cent. 

The influence of eucaine upon the general system is so slight that fifteen grains 
of it have been injected hypodermically (G. W. Spencer) without the production 
of any marked symptoms. It may prove of value in gastric pain or vomiting. The 
maximum dose is said to be three grains (0.2 Gm.). 

Tropacocaine. — This alkaloid was isolated by Giesel from the narrow-leaved 
coca-plant of Java. It is obtained as an oily liquid, which solidifies in radiating 
crystals, and is soluble in chloroform, ether, or petroleum benzin. It has been phys- 
iologically studied by Arthur P. Chadbourne, who finds that locally it acts in a 
manner similar to cocaine, without, however, causing ischemia or congestion of the 
mucous membrane with which it is brought in contact. It was found by Chadbourne 
to be only half as toxic as cocaine. In lower mammals it produces, in sufficient 
dose, loss of coordination, followed by violent convulsions, disturbances of the 
respiration, coma, and death by centric asphyxia. The convulsions are of cerebral 
origin. Upon the circulation the drug seems to have only a comparatively feeble 
influence, causing, however, when in sufficient amount, a steady fall in the arterial 
pressure. The temperature usually begins to rise before the convulsion, and has 



52 GENERAL REMEDIES 

been noted as high as 4° C. above t lie nornml. When tropacocaine is put in the eye, 
anesthesia is said to come on and disappear more quickly than with cocaine, sensa- 
t inn l>eing suspended in loss than half a minute after the application of a three-per- 
cent, solution: mydriasis is usually absent, never very pronounced. 

It is claimed for tropacocaine that it is especially superior to cocaine for the 
production of spinal anesthesia, being very much less likely to produce fever and 
other disagreeable symptoms (K. Schwarz and F. Neugebauer). According to 
Neugebauer, 0.05 to 0.06 gramme of the alkaloid may be injected. 

Orthoform is a white bulky powder very slightly soluble in water. It will 
not produce loss of sensation through the skin nor mucous membrane but is an 
efficient anesthetic when applied to raw surfaces. As it also possesses some antisep- 
tic power it is used chiefly as a dusting powder to burns or other painful wounds. 
In gastric ulcer it will at times greatly relieve the pain, for which purpose five to 
ten grains (0.3-0.6 Cm.) may be given at a dose. It is of great service in alleviat- 
ing pain in tuberculous laryngitis. 

Stovaine. — This benzoyl derivative was brought forward by Tourneau as being 
less toxic than cocaine. It has been used in spinal analgesia by Tuffier, who asserts 
that it is not followed by unpleasant after-symptoms. He injected one-half C.c. 
(8 minims) of a ten-per-cent. solution. It should not be used in connection with 
adrenalin. 

Practical Local Anesthesia. — If it were possible to prevent 
the absorption of one of the active local anesthetics, after its injection 
into a tissue, for a sufficient length of time, the method of local anes- 
thesia would be applicable to a very large proportion of surgical 
operations. When, as in the case of a felon, the part to be operated on 
can be tightly surrounded by a constricting bandage, so as to almost 
entirely shut off circulation, it is very easy to inject a local anesthetic 
and afterwards to operate without the production of pain. Rarely, 
however, is the surgical task so easy, and the several processes dis- 
cussed below have been invented for the purpose of overcoming the 
practical difficulties. 

Infiltration-Anesthesia. — In this process, as devised by Schleich, 
the original attempt was to increase the activity of cocaine by adding 
to its benumbing power the influence of the interference with the 
circulation of the part, and of pressure upon the nerve-trunks of the 
part, produced by the injection of large quantities of water directly 
into the tissue to be operated on. In this process, as originally devised, 
the skin having been frozen by means of an ethyl spray, the point of 
a large hypodermic syringe is thrust into its papillary layer and a small 
mass of the fluid is injected, not under, but into, the skin. The needle 
of the syringe is then pressed in a little deeper and a new injection 
made, the process being continued until a sufficient depth is reached. 
This method has been applied not only in minor but also in major 
surgery. During a large operation it may be necessary to repeat, 
from time to time, as the knife of the surgeon cuts more and more 
deeply into the tissues. 

Three solutions were used by Schleich. No. 1, of medium strength, may be 
made by dissolving, at the time of using, a powder composed of one and a half 
grains of cocaine hydrochlorate, one-third of a grain of morphine hydrochlorate, 



ANESTHETICS 53 

and throe grains of common salt In twenty-seven drachms of sterilized water. No. 
2, the weakest solution, contains only one-tenth the percentage of cocaine in No. 1; 
while No. 3, the strongest solution, contains double the percentage. No. 3 is used 
only when there is an active inflammatory lesion of moderate extent, as in case of 
a furuncle. In many cases it is essential that not only the part to be opened but 
the tissues beneath it be infiltrated. Thus, a furuncle or abscess may be completely 
encompassed with a zone of artificial oedema. 

A most important modification of the method of Schleich's infil- 
tration anesthesia has been brought to the notice of the profession 
by its inventor, H. Braun, who found that if, by local cooling, the 
vitality and circulation of a tissue be interfered with, absorption of 
the injected cocaine will be so long delayed that the symptoms of 
poisoning will be put off almost indefinitely or may fail to develop at 
all. Acting upon this knowledge, Braun obtained from the conjoint 
use of adrenalin and cocaine such satisfactory results as to apparently 
open a new field for the vise of local anesthesia: by employing a one- 
to five-per-cent. solution of cocaine to which had been added from 
1:10,000 to 1:100,000 of adrenalin, and beginning the operation 
from one to one and a half hours after the injection, he was enabled 
to do trunkal operations without causing suffering. 

Braun's method for the production of local anesthesia has been 
followed by so much of success by various surgeons* that it would 
seem to be demonstrated that adrenalin, by its powerful constringing 
influence upon the blood-vessels, not only very sensibly increases 
the benumbing action of the local anesthetic, but also, by lessening 
the rate of the absorption of the drug, greatly increases the duration 
of its local activity. The further suggestion of A. E. J. Barker, that 
the conjoint use of beta-eucaine and adrenalin affords a most excellent 
method of producing infiltration-anesthesia, has been followed out 
by various surgeons with great satisfaction. 

In his original discussion of infiltration-anesthesia, Schleich recog- 
nized that it was possible to produce a transitory anesthesia by infil- 
tration with pure water, and it has been shown by S. G. Gant that in 
cases of superficial abscesses and other surgical diseases, and in situa- 
tions in which injected water will for the time being, as it were, be 
dammed up in the tissues, it is possible to do painless minor opera- 
tions by simply throwing sterile water into the parts in such amounts 
as to produce great distention. The technique of the method is as 
follows: A fold of the skin on one end of the line of the incision is 
compressed between the thumb and forefinger, and then has slowly 
injected into it a few drops of water so as to produce a small, localized, 
blister-like distention. This is repeated until the whole line of incision 
has been gradually injected with water into, not under, the skin. 
The needle is plunged through this distended line, and subcutaneous 
injections are rapidly made until a firm, whitish, ridge-like swelling is 
produced, through which the incision can usually be made without pain. 

* See Braun, Cb. C, 1903; Honigman, Ibid.; Gangitans, B. M. J., 1903, ii.; Lefmann, M. M. 
W., 1902; Braun, A. K. C, Bd. lxix. 



54 



GENERAL REMEDIES 



The method seems to be especially applicable to rectal diseases. 
In external thrombotic hemorrhoids the water should be injected 
between the layers of the skin overlying the clot; in cutaneous hemor- 
rhoids both the skin and the tumor should be distended tightly; in 
external hemorrhoids each tumor must be distended so tightly as to 
cause it to turn white. In rectal operations the skin and subcutaneous 
structure up to the anal margin, then the mucosa and submucosa, 
the external and. if necessary, the internal sphincter muscle, must 




Fig. 4. — Showing Mode ok Injecting the Fluid under an Abscess in 
bbbive Whorls. (Schleich.) 

be distended with water slowly injected. In deep rectal operations, 
involving extensive cutting or curetting, water anesthesia seems not 
to suffice. 

Centric Local Anesthesia. — Corning, A. Bier, Seldowitsch, and 
Tuffier introduced into the practice of surgery the injection of cocaine 
into the spinal canal for the production of wide-spread anesthesia 
below the point of injection, and the method has been successfully 
employed, so far as the absence of pain is concerned, by various 




Fig. 5. — Showing the Syringe-point in the Papillary Layer of the Skin. 

surgeons in a large number of major operations in the lower portions 
of the body. Experience has, however, shown that this method is 
attended by so much difficulty and danger that it has almost passed 
out of vogue. 



In performing the operation the hollow needle is introduced into the vertebral 
canal, as in the operation of lumbar puncture, and from one-sixth to one-third of a 
grain of cocaine is injected, the most absolute antiseptic precautions being taken 
throughout. Loss of sensation in the lower extremities is usually complete in ten 
minutes and begins to go off in about an hour. Serious nervous disturbances have 
been present in a large proportion of the cases and fatal results have been frequent. 
One surgeon reported five deaths in one hundred intraspinal injections; and, ac- 
cording to H. Mohr-Bielefeld, all available statistics taken together show that one 
death is to be expected in every two hundred spinal anesthesias. 



ANESTHETICS 



55 



Much more available for the purposes of practical surgery than is 
centric anesthesia is the process which may be known as Neural 
Anesthesia. As long ago as 1884 the injection of cocaine into a nerve- 
trunk for the purpose of producing anesthesia in the region supplied 
by the nerve was suggested, not very clearly, by Hall and Halstead. 
In the production of neural anesthesia cocaine has been almost 
universally employed by surgeons, but whether it has or has not 
superiority over eucaine has not as yet been determined. The selected 
local anesthetic is to be injected immediately in contact with the 
nerve, if it be a small one, or into the nerve-trunk itself if the nerve 
be large. So injected, cocaine produces a complete break in the 
conducting power of the nerve, affecting, it is affirmed, not only 
the fibres which are connected with the pain sense, but all afferent 
fibres, so that, when the incision is made into the region of the periph- 
eral distribution of the nerve, not only is there no pain, but no 
surgical shock, all nervous impulses going upward from the lower part 
operated upon being shut off from the nerve-centres. When the nerve 
is small and easily reached, the injection of a two-per-cent. solution of 
cocaine may be made into its sheath without previous incision; but 
when an amputation or other large operation is to be performed, it 
is essential to expose under infiltration-anesthesia the one or more 
nerves involved, and inject a solution of cocaine, which should not 
be stronger than one per cent., directly into the centre of the nerve. 
When neural anesthesia is practised, it is essential that the most ab- 
solute antiseptic precautions be taken. A priori, it might be expected 
that the process would involve the danger of the production of 
neuritis, but so far the clinical reports do not indicate that such danger 
exists. 





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ANESTHETICS. 




ETHER. 


Neddorfan 


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NITROUS OXIDE. 


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Amort 


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Eulenberg. . 


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Great Britain, 1887, 


Hare 


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xix. 


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CvRTWRIGHT 


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Kratschmer. 
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W. A. W., 1870, Abt. ii 


COLTON 


C. B. S. A., 1890. 




tion of Nitrous Oxide 


Locke 


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Gas, Philadelphia, 




161 el ol. 




1871. 




A. G. M., 4 s., xiii. 374 


Goldstein 


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Chloroform, Phila.,1866 


Hermann 


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Schmidt 


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Hewitt 


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19. 


Jolyet and Blanche 


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Serres 


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Kemp 


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Waller 


B. M. J., Nov. 20, 1897 


Le Breton 


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Wittich 


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MacMunn 


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Wood 


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MacMunn 


The Spectroscope in 
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J. P., 1901, xxvi. 30. 


Ottlet 


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CHLOROFORM. 


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Bert 


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Thomson 


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Bert 


J. de l'A. and P., May, 


Van Arsdale 


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1870; C. R. S. B. 


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July, 1885. 




1893. 


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G. A. M. T„ 1895, 378. 


Wood 


.T. G., Aug. 1890. 


Bernstein. . . 


S. Jb., cxlii. 227. 



5G 



GENERAL REMEDIES 



REFERENCES (Continued). 



Bernstein U. N. M. T„ L870. 

Kihii.ls V.A.I'. A., 1892, c\\\. 

BLA1 i i B.K.C., 1901.xxxi.li71. 

Boxttchsb V. A. P. a., xxxii. I2(i. 

BOWDITCB ami .Misor.B. M. S. J., 1S74. 

Doi.hkai An. d'H., Jan. 1874. 

I y B. M. J., 1002. 

English Chloroform Committkk . I'roc. Royal 
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Gaskell and Sbobe. .B. M. J., 1893, i. 

Harley P. P. S. L., 1805. 



husemans. . 
Kafi-klek. . . 
Kai-peler. . . 



EbOobb. 

Leyden. 



MacWilliam. . 

Nlt'LOUX 

Noki 

nothnagel. . . 
Paugh 



.S. Jb„ cli. 84. 
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Berlin, 1866. 
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,C. R. S. B., lx. 1054. 
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Salkowski Fort. M., 1891, ix. 

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Simonin Cb. C, 1877, 234. 

Siolfatti Hif. M., 1895, i. 591. 

Sokolovski Z. P. C, viii. 

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Strassmann C. M. W.. 1888. 

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1893. 
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Wood U. M. M., July, 1898. 

Zeller Z. P. C, viii. 74. 



ETHYL CHLORIDE. 

Emblev Proc. Roy. Soc, 1906, 

lxxviii. 371. 

Lebet In. Diss., Berne, 1901. 

Malherbe and Roubinovitch, B. M., June, 
1902. 

McCardie B. M. J.. 1906, i. 616. 

Wood and Cerna Tr. P. C. M. S., 1892. 



ETHYL BROMIDE. 

Abonti Wiener Klinik. 1891, 

No. 1. 

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Cole B. M., 1903, i. 

Flatten Z. Mb., 1897, No. 7. 

Ginsburg In. Dis., St. Petersburg. 

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Gleich W. K. W., 1892 v. 

Reich Th. M., 1893. 

Scherbatscheff Th. M., 1889. iii. 

Suarez de Mendoza. .B. A. M., 1894. 
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PENTAL. 



Cerna. 



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.Trans. Texas State Med. 

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Ambrosius V. A. P. A., Suppl. 1895. 

Bandler S. Jb., cclii. 

Becker V. A. P. A., 1895, cxl. 

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Barker 

Bier 

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FAMILY III.— SOMNIFACIENTS. 



In the family somnifacients are placed in this treatise those drugs 
whose chief use in practical medicine is for the production of sleep. 
Hyoscine is a valuable hypnotic, but as it is found in plants associated 
with the delirifacient alkaloids, and is physiologically more closely 
allied to them than to the somnifacients, it will be considered under 
the head of Delirifacients. 

OPIUM. 

Opium is the dried juice obtained from the unripe capsule of the 
Papaver somniferum, the white poppy. This plant is a native of 
Asia, and was cultivated as far back as the time of Homer for the 
sake of its beautiful white flowers. The medicinal properties of the 
plant have been known for at least 2000 years, and Dioscorides has 
related the method of collection of opium, which is practically the 
same as that of to-day. The plant is extensively cultivated in India, 
China, Persia, and Asiatic Turkey. Immense quantities of it are 
produced, the importation of the United States alone being in the 
neighborhood of one and one-half million pounds annually. 

The Papaver somniferum is a small herb growing to the height of 
two to six feet, producing large, showy white flowers of a shape similar 
to that of our native red poppy. The active ingredient seems to be 
present in the plant only during fruition. Opium is obtained by 
incising the capsule (fruit) before it has ripened and allowing the 
juice to exude for twenty-four hours and then collecting. Several 
varieties of opium are recognized according to the country from which 
they enter commerce, as the India opium, the Persia opium, etc. 
Practically all of the opium which enters the United States comes 
through the port of Smyrna and is known as Turkey opium or Smyrna 
opium. It occurs in large, irregular lumps, weighing from a quarter 
to two pounds, of a brownish, mottled color, frequently with the 
remnants of poppy-leaves or plants adhering to its surface. It has a 
peculiar "narcotic" odor and a bitter taste. It is completely soluble 
in dilute alcohol, and although not completely dissolved, its active 
ingredients are taken up by water. It is a very complex body, con- 
taining the alkaloids morphine, codeine, narceine, narcotine, thebaine, 
papaverine, porphyroxine, cryptopine, meconine, opianine, and 
paramorphine, besides meconic, thebolactic, and sulphuric acids, 
extractive matter, gum, glucose, fixed oils, a volatile odorous principle, 
and other substances of no importance. Of these substances morphine 

57 



58 GENERAL REMEDIES 

is by far the most important and the U. S. Pharmacopoeia directs 
that crude opium shall contain not less than nine per cent, of this 
alkaloid. 

Morphine is obtained by precipitation with ammonia water from 
solution of opium. It is very slightly soluble in water, but, like the 
other alkaloids, forms soluble salts with various acids. 

Incompatibilities.— Opium is incompatible with the alkaloid 
precipitant.-;, as alkalies, tannic acid, corrosive sublimate, iodides, etc. 
Besides these, on account of the meconic acid, it precipitates the salts 
of many metals, notably lead acetate (which is the basis of the well- 
known lead-water and laudanum embrocations). 

Official Preparations:* 

There are six solid preparations of opium: 

Opii Pulvis (12 per cent. Morphine) i to 2 grains (0.03-0.12 Gm.). 

( Ipium Deodoratum (12 per cent. Morphine) . I to 2 grains (0.03-0.12 Gm.). 
Opium Granulatum (12 per cent. Morphine). J to 2 grains (0.03-O.12 Gm.). 

Pilulffl Opii (Each one grain) 1 to 2 pills. 

Extractum Opii (20 per cent. Morphine). . . J to 1 grain (0.03-0.06 Gm.). 
Pulvis Ipecacuanha? et Opii [Dover's 

Powder] (10 per cent, each of ipecac 

and powdered opium) 5 to 10 grains (0.3-0.6 Gm.). 

The liquid preparations each represent ten per cent, powdered opium, except 
the camphorated tincture. It. should be remembered that one minim of tincture 
of opium is equal to almost two drops. 

Acetum Opii (10 per cent.) 5 to 15 minims (0.3-1.0 C.c). 

Tinctura Opii [Laudanum] (10 per cent.) ... .5 to 15 minims (0.3-1.0 C.c). 

Tinctura Opii Deodorata (10 per cent.) 5 to 15 minims (0.3-1.0 C.c). 

Tinctura Opii Camphorata [Paregoric] (Pow- 
dered opium, camphor, benzoic acid, oil 
of anise, each 0.4 per cent.) 1 to 4 fluidrachms (4-15 C.c). 

Vinum Opii [Sydenham's Laudanum] (10 per 

cent.) 5 to 15 minims (0.3-1.0 C.c). 

Tinctura Ipecacuanha; et Opii (10 per cent. 

of each) 5 to 15 minims (0.3-1.0 C.c). 

The following preparations of Morphine are recognized: 

Morphina £ to \ grain (0.008-0.015 Gm.). 

Morphina; Acetas \ to \ grain (0.008-0.015 Gm.). 

Morphina; Hydrochloridum £ to \ grain (0.008-0.015 Gm.). 

Morphina; Sulphas \ to \ grain (0.008-0.015 Gm.). 

Pulvis Morphina; Compositus [Tully's 

Powder] (1 \ per cent.) 5 to 10 grains (0.3-0.6 Gm.). 

The official salts of codeine are: 

Codeina \ to 2 grains (0.03-0.12 Gm.). 

Codeinae Phosphas A to 2 grains (0.03-0.12 Gm.). 

Codeina; Sulphas \ to 2 grains (0.03-0.12 Gm.). 

Local Action. — The local action of opium and its chief alkaloid 
appears to be purely sedative. 

* For morphine derivatives see page 73. 



SOMNIFACIENTS 59 

Elimination — Morphine, according to Cloetta, is largely destroyed 
in the system, but it is also partly eliminated through the various 
glands, especially the kidneys and the glands of the stomach and 
intestines. 

Morphine has been detected in the urine by Eliasson, Bouchardat, Wormley, 
■ and many others; in the alimentary secretions by Orlt, Rosenthal, Binet and Ham- 
lierger. The elimination appears to proceed slowly, as Wormley detected the alka- 
loid in the urine passed three days after its ingestion, and Antlieaume and Mouneyrat 
found it in the body of an opium-eater who had died fourteen days after the last 
dose. Faust believes the alimentary glands are the most important channels of 
escape of the drug. 

Physiological Action. — Nervous System. — When opium is taken 
by man in such dose as to produce its mildest physiological effects, 
it exerts a quieting influence, inducing a peculiar dreamy condition 
of bodily comfort and happy content, during which images and ideas 
float before the mind, and by their endless and effortless repetition 
shorten the time, which seems to lose itself in rest. It is commonly 
asserted that there is a stage of the action of opium in which the 
activity of the mental faculties is exalted. This may be so in those 
who have accustomed themselves to the use of the drug as a stimulant; 
but our experience is that in those who do not habitually take opium 
true mental power is, during all the stages of the action of the drug, 
diminished rather than increased. The state induced is the fabled 
calm of the lotus-eater rather than the energetic activity of production. 
Even in those who are accustomed to the use of opium, as an aid to 
work, it is probable that the imagination rather than the reasoning 
faculty is excited by it. 

The apparent difference in the effects of morphine upon man and 
the lower animals depends chiefly upon the different degree of develop- 
ment of the brain and spinal cord. The drug acts as a cerebral depres- 
sant and a spinal stimulant, and in the lower scale of life, where the 
spinal cord is more highly developed than the cerebrum, it produces 
exaggerated reflexes and convulsions, whereas in the higher mammals, 
as in man, the cerebral symptoms predominate as is shown by quietness 
and sleep.* 

In the frog, opium and morphine act similarly, producing primarily a condition 
of violent tetanus, with great increase of the reflex activity, ending, if the dose has 
been large enough, in a progressive paralysis with disturbed respiration, and finally 
cessation of the same. W. Baxt states that when a very minute dose is used (15.25 
milligrammes) after a period of heightened excitability there is stupor with in- 
creased reflex excitability as it passes off. As was first shown by Kolliker, and 
abundantly demonstrated since, the tetanus is not prevented by section of the 
spinal cord, and, with the heightened reflex activity, is therefore due to spinal 
excitement. It is probable, however, as affirmed by Kolliker, by Albers, and by 
Meihuizen, that some of the convulsions are epileptiform. 

* A curious corroboration of the views expressed in this paragraph is found in the following 
sentence taken from Althaus (Diseases of the Nervous System, New York, 1878, 135): "In infants, 
however, and also in the lower races of mankind, as in negroes and Malays, convulsions are observed 
after its [opium] ingestion." 



60 GENERAL REMEDIES 

S. Weir Mitchell has shown that birds, as represented by pigeons, chickens, 
and ducks, are very insusceptible to the toxic action of opium and its chief deriva- 
tive, morphine. The symptoms induced have been very uniform: they are un- 
steadiness, labored breathing, increasing signs of dyspnoea, unaltered pupils, and, 
finally, general convulsions and death. No true hypnotic effect has been observed, 
but a curious and very great rise of temperature just before death was noted in one 
case. As llouiens affirms that a single grain of the aqueous extract of opium will 
throw a sparrow into a profound stupor, it can scarcely be considered as proved 
that the drug acts upon all birds as upon those experimented with by Mitchell. 

In the mouse, according to the experiments of Harley, the first effect of an 
injection of from one-twentieth to one-twelfth of a grain of morphine is a tonic 
cramp-like contraction of the muscles, especially of the trunk, of such character 
that periods of forced rest alternate with a slow, laborious creep, which seems to 
originate not in the limbs but in the trunk itself. There is in this state no tendency 
to somnolency, but, on the contrary, an abnormal sensitiveness to loud sounds, 
which cause the mouse to resume for a moment active running movements. The 
breathing is irregular, the pulse accelerated, and finally stupor develops itself, and 
coma deepens into death by dyspnoea; or, otherwise, recovery, preceded by con- 
vulsive movements of the hinder part of the body, is gradually brought about. 

According to M. L. Guinard, in the cat morphine produces violent hyper- 
excitability, great restlessness, agitation, hallucinations, dilated pupils, accelerated 
heart and respiration, from which the animal returns to its normal condition unless 
the dose have been very large, when tetanic convulsions develop. 

In the horse (Harley) two or even three grains of morphine hypodermically 
injected produce sometimes a slight drowsiness, sometimes no perceptible effect. 
Doses of from four to six grains cause great restlessness and accelerated pulse. 
The mouth is moist, the temperature of the skin and its secretion increased; the 
animal paws continually, and treads about in his stall with an almost rhythmical 
movement. After twelve grains, Harley noticed in some cases very great excite- 
ment, as shown by marked increase in the rapidity of the heart's action, by mus- 
cular rigidity and tremors, and by the animal's walking rapidly to and fro, slobber- 
ing and sweating profusely. In another horse, after an immediate strong erection 
of the penis and copious emission of semen, heavy sleep came on, interrupted after 
t he third hour by the usual symptoms of excitement. Thirty-six grains of mor- 
phine acetate caused in a powerful hunter deep comatose sleep, commencing in 
fifteen minutes and lasting for three hours, when it was replaced by intense restless- 
ness and severe delirium, continuing for seven hours. During this time the animal 
was perfectly blind. Previously to these studies, Barbier had found that four 
drachms of the aqueous extract of opium produced violent tremblings, apparent 
insensibility to external irritants, convulsions without coma, and death. One hun- 
dred grains of morphine acetate killed a horse by convulsions in three hours. Ernst 
Hess has shown that in the ruminants morphine produces first excitement and 
then narcosis. 

Upon dogs* morphine acts very much as upon man (see Harley, Bernard and 
Reese). In very many cases, if not in the majority, eight to ten grains of the alka- 
loid injected into a dog of moderate size will cause deep sleep, amounting to coma, 
so that the animal will remain in any position in which he may be placed. While 
in the deeper degrees of this sleep there is marked insensibility to pinching and 
other forms of external irritation, a repetition of irritation, and especially a sudden 
loud noise or shaking, will arouse the animal, precisely as in man. Indeed, some- 
times the dog, even when comatose, seems more than normally sensitive to sudden 
noise, trembling and starting in an almost convulsive manner. After awaking, 
the dog shows unmistakable signs of nervous and psychical depression. In walking, 
the hind legs are dragged, as though semi-paralyzed; the eyes are haggard; the 
naturally brave animal cowers in a corner or seeks to hide himself, no longer recog- 

* According to Joflroy and Serveaux (Archiv d. Med. Exper. Anal. Path., 1898, x.>, the fatal 
dose of morphine is: for dogs, intravenously 0.029 gramme per kilo, hypodermically 0.035 per kilo; 
for rabbits, intravenously 0.15 per kilo, hypodermically 0.25 per kilo. 



SOMNIFACIENTS 61 

nizing his master, and docs not. return to his natural condition for many hours. 
After smaller doses the effects arc proportionately less intense. 

Nerves. According to Cischeidlcn, morphine primarily increases and second- 
arily depresses the excitability of the motor nerves of the frog, the period of height- 
ened functional activity not being demonstrable after enormous closes. Albcrs 
a Hinns that depression may develop into complete paralysis of function, though 
Gscheidlen has never been able to verify this. Gscheidlen further asserts that the 
local application of morphine intensifies and protracts the excitability of an afferent 
nerve in strychnine-poisoning. No phenomenon of human poisoning by opium 
can be attributed to its action on nerve-trunks, but the relief of pain sometimes 
obtained by the local use of opium would indicate that in concentrated form it 
depresses the sensory fibres even of human nerves. 

Circulation. — In man a moderately large dose of opium produces 
a slight evanescent acceleration of the pulse-rate (see Nothnagel) 
succeeded by a characteristic slowing and increased fullness and force 
in the pulse. After toxic doses the slow pulse later becomes exceed- 
ingly rapid. In the lower animals large doses produce a slight rise 
in the blood-pressure followed, after poisonous quantities, by a fall. 
The slowing of the pulse is due to stimulation of the cardio-inhibitory 
mechanism, probably chiefly central, although Gscheidlen believes 
that the peripheral endings of the vagi are also stimulated. The 
increased rate of the pulse in poisoning is due to paralysis of the 
peripheral ends of the vagi. The changes in the arterial pressure are 
due chiefly to its influence upon the heart muscle, the drug acting 
in moderate quantities as a slight stimulant, in larger doses exercising 
a depressant influence upon the heart; its action upon the vaso-motor 
system is uncertain but is probably very slight, if any. The thera- 
peutic dose of morphine in man produces practically no change in 
the circulation aside from some slowing of the pulse. 

In some individuals therapeutic amounts of the alkaloid may depress the cir- 
culation, but, in agreement with Riegel and Preisendorffer, it can scarcely be doubted 
that therapeutic doses have no sensible effect upon the circulation in the ordinary 
man. It has been found by M. L. Guinard that in the dog morphine produces 
primarily a slight rise of the arterial pressure, followed by a fall during the period 
of narcosis. Ringer and Sainsbury found that opium first increased the power of 
the isolated heart of the frog, then depressed it and finally caused diastolic arrest. 

The slow, full pulse of the second stage of opium-poisoning is due to an action 
of the drug upon the inhibitory cardiac nerves, for Gscheidlen has experimentally 
demonstrated that after section of the vagi morphine is powerless to lower the 
pulse, and also that division of the nerves during the second stage of morphine- 
poisoning is followed by an extraordinary rise in the pulse-rate. That the periph- 
eral ends of the vagi are stimulated was proved by the fact that cardiac arrest 
took place when the distal ends of the cut nerve were more feebly irritated than 
would suffice to affect the unpoisoned animal; and that the inhibitory cerebral 
centres are stimulated was demonstrated by the instantaneous very great fall of 
the pulse-rate, amounting in some cases to one-half in less than half a minute, which 
ensued upon the injection of a large dose of the alkaloid into the carotid, — i.e., 
into the brain and the inhibitory centres. The rapid feeble pulse of the third stage 
of opium-poisoning Gscheidlen found to be due, at least in a measure, to paralysis 
of the peripheral vagi; for at such time stimulation of the peripheral end of the cut 
nerve was powerless to affect the heart. 

The question of the action of morphine upon the vaso-motor system is of great 
interest, but cannot at present be fully answered. Gscheidlen believes that it first 



82 



GENERAL REMEDIES 



-timulates and then depresses it, and asserts that after the injection of a large dose 
the arterioles in the mesentery can be seen to contract, and later (third stage) to 
dilate. The objections to this sort of evidence are sufficiently stated elsewhere in 
this book; and the rise of the arterial pressure, which he also adduces as an argu- 
ment, may be accounted for without calling upon the aid of the vaso-motor nerves. 
While, therefore, it is probable that morphine does exert the influence he asserts 
for it, the quest ion must st ill l>e considered as sub judice: that the vaso-motor system 
is not paralyzed even in extremis is shown by Gscheidlen's experiment, in which 
electrical stimulation of the cord at such time induced immediate rise of the arterial 
pressure. The action of morphine upon the brain is certainly independent of any 
action on the vessels.* 




(Before Injection.) 



(After Injection.) 



Fig. 6. — The Effect of Opium on Circulation and Respiration. Note the great slowing of 
respiration, also the slowing of the pulse without much change in the blood-pressure. 

Respiration. — Death occurs from opium, in the great majority 
of cases, by failure of the respiration; and that such failure is due to 
a direct action of the poison upon the respiratory centres in the medulla 
is proved by the fact that morphine affects the breathing of dogs 
and rabbits whose pneumogastrics have been cut as much as it does 
those whose nerves are entire (Gscheidlen). 

The action of opium or morphine upon the elimination of carbonic acid has 
been studied by Boeck and Bauer and by Chittenden and Cummins. Their results 



♦Consult Binz, Arch. /. Exper. Pathol, und Pharm., vi. 310; Vulpian, Lecnns sur VAppar. 
vaio-moteur, ii. 150. 



SOMNIFACIENTS 63 

are concordant in showing that the effect of the alkaloid upon carbonic acid pro- 
duction is in direct relation to its influence upon the muscular system. The elimi- 
nation is increased when convulsions occur, but decreased when narcotic quietude 
is produced. According to Reichert, the fall of temperature produced by the toxic 
dose of morphine is caused by a lessening of heat production, which is due to depres- 
sion of thermogenic centres in the caudate nucleus. Luzzatto found that under 
the influence of morphine there is a very marked increase in the destruction of 
nitrogenous tissue. 

Eye. — Since morphine locally applied does not affect the pupil, 
it follows that its contracting action upon the latter is through the 
nerve-centres. It is probable, but has not, that we are aware of, been 
experimentally proved, that the contraction of the pupil is, at least 
largely, due to stimulation of the oculo-motor nerve-centres, and that 
the dilatation of the pupil as death approaches is due to a paralysis 
of the same. Indeed, it cannot well be otherwise; for if the primary 
contraction were due to paralysis of the sympathetic, the secondary 
wide dilatation would be impossible; the dilating force — i.e., the 
sympathetic — having been withdrawn, the pupil would not widely 
expand even if the contracting force — i.e., the oculo-motor — were 
paralyzed. 

In birds (S. Weir Mitchell) the pupil is not affected, probably for anatomical 
reasons (see Atropine). In horses it is widely dilated (Harley); and in dogs it 
dilates before contracting (Reese, apparently confirmed by Experiment No. 8, 
Harley), or sometimes remains unchanged (Harley). At present these anomalies 
cannot be explained. 

Secretions. — Opium ordinarily checks all the secretions of the body, 
although this influence is capable of being modified by certain drugs 
so as to produce a sudorific action. By it the urinary secretion is 
habitually diminished, owing, as has been shown by Thompson, to a 
direct action upon the kidneys. Retention, which after a full dose 
of opium is not rare, depends upon the blunting of the sensibility of 
the bladder. 

Intestines. — Opium, and to a less extent morphine,* has a very 
pronounced influence upon the digestive tract, in many persons 
producing nausea, in all lessening the appetite and the activity of 
digestion and causing constipation. The disorder of digestion and 
the constipation are in part, at least, due to an arrest of secretion, 
probably both in the stomach and in the intestines; but they are 
also probably to some extent due to the checking of peristalsis, an 
effect which can often be shown in men, and which Nothnagel and 
Ott have demonstrated upon animals. f According to Magnus, the 
effect on peristalsis occurs after dividing the plexuses of the nerve 
trunks passing from the sympathetic system to the intestines. He 

* Vamossy {Deutsche Med. Wochensch., 1897, xxiii.) has endeavored to determine experi- 
mentally why opium causes constipation more than does morphine. He finds, however, that 
neither narcotine, thebaine, codeine, kryptopine, nor laudanine is equal in power of checking 
peristalsis to morphine; and that it is not probable that any of them are responsible for the consti- 
pating effects of the crude drug. 

t The theory of Hirsch, that morphine causes contraction of the pylorus, is very improbable, 
since, granting the correctness of his experimental results, a more probable explanation is that 
gastric peristalsis is checked by the alkaloid. 



64 GENERAL REMEDIES 

believes the action is upon the plexus of Auerbach. Both Nothnagel 
and Ott affirm that the toxic dose of morphine in the lower animals 
increases peristaltic movement, which affords a possible explanation 
of the diarrhoea sometimes seen in chronic opium-eaters. 

SUMMARY.— The dominant action of opium is the production 
of sleep by cerebral depression. The power of relieving pain is as 
yet not thoroughly explained ; probably, however, by benumbing the 
perceptive centres in the brain. It acts upon the spinal cord of 
many of the lower animals as a stimulant, but in man this effect is 
not perceptible. It both slows the pulse and increases to some ex- 
tent the force of the circulation by an action upon the inhibitory 
nerve-centres, probably both centric and peripheral, and by a slight 
stimulant influence upon the heart-muscle or its intrinsic ganglia. 
It is a centric respiratory depressant; it contracts the pupil by a 
centric action which is probably that of stimulation of the oculo- 
motor nerve-centres. It lessens all the secretions except the sweat 
and also diminishes intestinal peristalsis. 

Therapeutics.— The chief indications for the use of opium 
are considered below, seriatim. Nearly all of them flow evidently 
from the known physiological action of the drug; others, however, 
although established by clinical experience, and undeniable, are not 
so plain in their philosophy. 

1. To relieve pain. — As an analgesic, morphine is without a rival 
in the materia medica, except it be the anesthetics. It is used to 
allay pain arising from any cause whatever, except acute inflammation 
of the brain, and is preferred to the anesthetics whenever the pain 
has any permanency. In painful spasm it is especially useful, as it 
seems very frequently to quiet the motor as well as the sensory 
disturbance. 

, 2. To produce sleep. — Sleeplessness occurring in acute disease, and 
not dependent upon cerebral inflammation, may very frequently be 
relieved by morphine. While it is often necessary to use the drug 
freely in such affections as delirium tremens, care should be exercised 
not to overwhelm the nerve-centres by enormous doses. In habitual 
sleeplessness great caution must be used in the employment of mor- 
phine, not so much on account of the disturbance of digestion which 
it is liable to cause, as for fear of producing the "morphine habit." 
Chloral is perhaps a more generally applicable hypnotic than opium. 
Be this, however, as it may; we have found the combination of mor- 
phine and hydrated chloral singularly efficient. In low fevers, ady- 
namic delirium often coexists with sleeplessness, and is then best 
met by morphine. 

3. To allay irritation. — In various forms of nervous erethism, 
morphine is most valuable; but when the affection is at all chronic, 
the dangers of the opium habit should not be lost sight of. On the 
other hand, in acute cases, as in the excitement which so frequently 
attends hemoptysis, the drug should be used freely. In many cases 



SOMNIFACIENTS G5 

of disease, opium is serviceable by sustaining the system against an 

irritation for the time 1 icing irremediable, by blunting the sensi- 
bilities. In this way it is useful in the advanced stages of smallpox, 
and in various surgical affections, in which it also does good by allay- 
ing pain. In various local irritations opium is continually employed, 
as in colic caused by undigested food, and in bronchitis to quiet cough. 

By allaying irritation and pain, morphine affords relief in most 
cases of inflammation; but in certain varieties of the affection it seems 
to do much more than this, exerting, in some way at present difficult 
to explain, a life-saving influence. In peritonitis, after due depletion, 
or in cases not requiring depletion, it should always be exhibited in 
large doses at regular intervals, in such a way as to keep the patient 
in a state of decided narcotism. 

In severe acute vomiting, opium is one of the most reliable remedies. 
Although, by checking secretion and peristalsis, opium usually causes 
constipation, yet when obstruction of the bowels is produced by spasm 
due to an irritation or inflammation, by relieving the latter morphine 
will sometimes act as a most efficient laxative. 

4. To check excessive secretion. — For this purpose opium is very 
largely employed in diarrhoeas, and is very efficient either alone or in 
combination with various remedies. In enteritis and in dysentery, 
although no less frequently used than in diarrhoea, it is of service as 
an antiphlogistic and analgesic rather than by checking secretion. 
In diabetes insipidus, the combination of it and gallic acid has been 
much used, and is often effective. 

In diabetes mellitus opium has long been employed as one of the 
most useful remedies we have for this disease. Meyer reports a case 
of diabetes due to pancreatic cancer in which opium produced a 
diminution in the daily output of sugar. While in some cases it 
appears to have effected a permanent cure, in the majority of in- 
stances, like all other known remedies for this disease, it acts simply 
as a palliative; it must be given in large ascending doses, the patient 
for the time being made an opium-eater, a procedure justified only 
by the fatal nature of the malady. In this condition opium is prefer- 
abh to morphine. Many authorities have claimed to have obtained 
the same results from codeine with less derangement of the intestinal 
tract. 

5. To support the system. — Opium appears in low fevers, and in 
various protracted adynamic illnesses, to afford actual support to the 
system in some way not as yet made out. This is especially the case 
when, from any reason, sufficient food to keep up life cannot be taken 
or retained. Opium is a valuable remedy for the purpose of pro- 
tracting and rendering more comfortable life in the aged. When the 
bodily powers are failing, and various functional disorders are from 
time to time occurring, it is often possible to check, by the use of 
opium, attacks which, if allowed to obtain headway, would extin- 
guish the nickering life. Further, in many cases of feeble very old 
and suffering people the habitual use of opium under careful restric- 

5 



Go GENERAL REMEDIES 

t ion of the physician is not only justifiable, but necessary if life is 
to be maintained as long as possible. In such persons the danger 
of forming an opium habit which shall do injury is reduced to a 

minimum. 

(i. As a sudorific. — In 1873 A. Loomis stated that in acute uremia 
large hypodermic injections of morphine would control the convul- 
sions, at the same time producing a profuse diaphoresis, which has been 
confirmed by Fiset. The method of treatment has been largely 
followed, in some instances with very happy effect, but in other 
has apparently produced death. Whenever the kidneys are 
seriously diseased the free administration of opiates is attended by 
much danger, because one of the chief channels through which the 
opium alkaloids escape from the system is choked up. As a general 
sudorific opium is used almost exclusively in the form of Dover's 
powder. (See p. 58.) 

Administration. — When it is desired to produce the systemic 
effect, morphine is usually preferable to the cruder preparations of 
opium. Pills of opium are especially to be avoided because they 
sometimes become very hard and undergo solution so slowly that 
their accumulation in the alimentary canal is possible. On the other 
hand in the treatment of diarrhoea opium will be found to be more 
constipaling than its alkaloid. 

.Many persons cannot take opium on account of the very great 
secondary nausea and depression which it produces. It has been 
supposed that these disagreeable after-effects are due to the nar- 
cotine in opium; but this can hardly be, seeing that they often fol- 
low the use of the pure alkaloid, morphine. The deodorized tincture 
of opium agrees with some individuals better than any other prepa- 
ration of the drug; and, as first pointed out by Da Costa, by giving 
a drachm of potassium bromide with twenty-five minims of it, the 
after-effects of the narcotic are often entirely avoided. Nitroglycerin 
in many cases will also lessen the gastric disturbance. 

Children always bear opium very badly,* and to them only the 
weaker liquid preparations should be given. Dover's powder should 
especially be avoided. It is probable that in its manufacture on the 
large scale the ingredients are sometimes not thoroughly mixed: 
at least we have seen cases in which the symptoms caused by it were 
seemingly so out of proportion to the dose as to suggest that more 
than the official amount of opium was present. 

The dose of opium for an adult is from one to two grains (0.06- 
0.12 Gm.); for a child a vear old, one-twenty-fourth of a grain (0.003 
Gm.). 

Of the solid preparations of opium the extract on account of its 
being the most fixed in its strength as well as of its being free from 
the noxious constituents of opium, and of its solubility favoring 

* In a babe a day old, one minim of laudanum (K. Smith, Laurel. 1S. r >-4 >, and in one aged nine 
months, a few minims of paregoric (Wood, Bost. Med, and iSurg. Jowrn., 1858', are said to have 

proved fatal. 



SOMNIFACIENTS 07 

prompt absorption, is the most useful and reliable. Paregoric, because 
of the camphor which it contains, is more constipating than are the 
other preparations of opium, and hence is preferred in diarrhoea- 
mixtures. The deodorized tincture contains no nareotine, and none 
of the odorous principle of opium and, therefore, is less apt to cause 
nausea than are the other preparations. Its drop almost equals the 
minim in size. 

Toxicology. — After the ingestion of poisonous doses of opium 
or its alkaloid morphine, there is a period, the duration of which is 
in inverse ratio to the dose ingested, in which there is a pleasant 
feeling of exhilaration and languor with perhaps a slight increase in 
the rate and force of the pulse, and sometimes nausea and even 
vomiting. The condition of languor passes gradually into a com- 
plete sleep. The increase in the pulse-rate, if it occur at all, is only 
transient. The characteristic symptoms of opium-poisoning at the 
stage when the case is usually seen by the physician closely resemble 
those of cerebral congestion, indeed they are sometimes indistinguish- 
able. The patient is asleep but usually can be partially aroused by 
loud noises, shaking, cold water and other means, but when left to 
himself immediately drops to sleep again; the pupils are contracted, 
the face flushed, sometimes slightly cyanosed, the skin is generally 
dry and warm, respirations are slower than normal but usually fairly 
deep and regular. When the patient is aroused the respirations 
become more rapid and the skin regains almost at once its normal 
color, the pulse is slow, full and strong. Death very rarely occurs 
during this stage. If the symptoms do not gradually ameliorate the 
patient passes into a condition of stupor and prostration, the sleep 
becomes comatose in character so that it is frequently impossible to 
arouse him, the pupils are contracted almost to obliteration, the skin 
becomes cold and moist, the face is at once pallid and cyanosed, the 
respirations extremely slow and shallow and often interrupted by 
intervals of death-like quiet, the pulse rapid and feeble, and gradually 
the patient dies with extinction of nearly all the vital functions, 
although the immediate cause of death is usually respiratory failure. 

The most important points in the diagnosis are the equally con- 
tracted pupils, the character of the sleep, and the slowness of the 
pulse and the respiration. 

Although the symptoms which have been narrated are those usually produced 
by opium, yet in certain individuals the drug provokes quite different phenomena. 
Thus, cases have been reported in which one-fourth of a grain, or a somewhat greater 
quantity, of morphine, hypodermically injected, has been followed at once by 
syncope, with struggling for breath, and apparently imminent or even present 
death.* A rarer idiosyncrasy exists in those persons who are rendered by opium 
very delirious, it may be even wildly so. In certain cases of opium-poisoning, 
partial or complete convulsions have occurred amidst the more usual phenomena.! 
Severe itching of the skin is a common phenomenon when the action of opium is 

* See Report of the Committee on the Hypodermic Method of Injection, Medico-Chirurgical 
Transactions, i.; see also Medical Times and Gazette, 18(18. cases reported by Braine and by Roberts. 
t Cases, Brit. Med. Jou.ni., 1876, ii. 490; Pacific Med . and Surg. Journ., July, 1876. 



68 GENERAL REMEDIES 

going off, and there are persons in whom such violent erythema is produced even 
by therapeutic doses as to forbid its use. R. V. Jaksch reports temporary blindness 
as produced by opium. Glycosuria has been noticed both in animals and man 
(Adler; also Luzzatto). 

The positive medico-legal diagnosis of opium-poisoning from the symptoms 
alone is not possible, even in the most characteristic cases, because the phenomena 
produced by cerebral congestion, apoplexy, and uremia may be identical with those 
of opium-poisoning. Inequality of the pupils, which has been considered proof 
that a case is not narcotism, lias been reported by Taylor as present in poisoning. 
In atypical cases without a history, even the working diagnosis may be very difficult. 
The spinal symptoms may entirely overshadow the cerebral phenomena; trismus, 
tetanic convulsions, tonic rigidity of the muscles, spastic gait, marked heightened 
rellc\<s, and ankle clonus have ln-cn reported by the drug in the adult. In children 
it is common for the nerve-centres to be at once overpowered by the poison, so 
that the second stage may be very much shortened or entirely aborted, and collapse 
with unconsciousness develop almost at once.* 

Treatment of Opium-Poison.— Tannic acid is feebly antidotal to 
morphine, but it has been entirely displaced by potassium perman- 
ganate, which rapidly destroys the alkaloid by oxidation. The 
allegation that potassium permanganate is capable of following 
morphine into the blood and there destroying it is, a priori, improb- 
able, and it has been experimentally shown that the hypodermic- 
injection of potassium permanganate in morphine-poisoning is futile 
(Sharp and Thornton and Holder). Nevertheless, during the whole 
narcosis, there should be repeated administrations of potassium 
permanganate by the mouth for the purpose of destroying morphine 
excreted into the stomach. Besides the administration of the anti- 
dote, the indications in opium-poisoning are to evacuate the stomach, 
to maintain respiration, and to keep up the circulation when failing. 
The first of these indications may be met in two different ways: 
by an emetic, and by the stomach-pump or tube used as a siphon. 
There is often in narcotic poisoning great difficulty in getting an 
emetic to act, owing to the obtunding of the sensibility of the ner- 
vous system by the poison. For this and other reasons, so palpable 
as not to need mentioning, only a prompt stimulant emetic should bs 
used. Antimony, on account of its depressing influence, should al- 
ways be avoided. Mustard flour is almost always to be had at once, 
and is very efficient. A heaped tab espoonful stirred up in a tumbler- 
ful of warm water should be exhibited as soon as possible, and, if 
it fail to act in fifteen minutes, should be repeated; if this fail, a 
powder of thirty grains each of zinc sulphate and ipecacuanha may 
be given, to be repeated at intervals of twenty minutes. Large 
draughts of warm water should be administered in the intervals, 
and also between the acts of vomiting, so as thoroughly to wash out 
the stomach. The stomach-pump j is of no value when the solid 

* For discussion of effect on nursling and fcetus when morphine is given to the mother, see 
Amer. Journ. Obslet., 1877. 

t The siphon stomach-pump may be readily extemporized. It consists simply of an india- 
rubber tube three and a half to four and a half feet in length, of proper calibre, which is passed 
into the stomach. The external end being elevated, water is poured into it until the stomach is 
full; then, without the tube being allowed to empty itself, the external end is dropped, when, of 
course, the flow of water is reversed. 



SOMNIFACIENTS 69 

drug has been ingested, but, if a1 hand, is preferable to emetics when 
:i liquid preparation has been taken, because of the promptness and 
thoroughness of its results. 

To maintain respiration is the ultimate object of all the measures 
which are commonly undertaken for the purpose of arousing the 
system in opium-poisoning. Unconsciousness in itself is of no mo- 
ment, but as it deepens the sensibility of the respiratory centres 
grows less, and consequently the involuntary breathing is less rapidly 
or less perfectly performed. More than this, when at all awake, a 
patient suffering from opium-poisoning can be made to supplement 
the almost suspended automatic breathing by voluntary respiration, 
and every effort to induce him to do this should be used. It is often 
surprising how an apparently unconscious man can be made to breathe 
by a command shouted in his ear. To keep a patient awake, walking, 
flagellations with small, fine twigs, shaking, shouting, and various 
other methods which may suggest themselves, should be practised. 
Care should always be exercised not to carry these useful measures 
unnecessarily far, and perhaps add physical exhaustion to the nat- 
ural prostration of the third stage. The strong faradic current 
offers a means of causing pain, and therefore of rousing the patient, 
without leaving bruises or other after-effects. 

The cold douche is also an excellent method of rousing the patient 
and at the same time of especially stimulating respiration. The 
simplest method of application is to support the head and shoulders 
of a patient, stripped to the waist, over a common wash-tub, and to 
dash the water over the chest and head. The effect is much greater 
if ice-cold water and water a little hotter than the hand will bear 
(115° F.) be used in quick succession. Very strong coffee has been 
used from time immemorial, and may be substituted by the alkaloid 
caffeine. The alkaloids which are to be relied upon, however, are 
strychnine, cocaine, and atropine, and of these the most valuable 
is probably strychnine, next cocaine.* The .alkaloids should be 
given hypodermically, in moderate doses at short intervals, until 
some effect is manifested upon the respiration. The pupil is not 
a safe guide as to the administration of atropine, which alkaloid 
should, indeed, never be given in very large doses. In all cases it is 
better to use two or more of these alkaloids than larger doses of any 
one. When in advanced stages the circulation fails, digitalis and 
strychnine are the chief remedies, but alcohol may be used carefully, 
the danger being that any excess of it may aid in depressing the heart. 
In severe cases it is wise to give digitalis hypodermically before the 



* The value of strychnine as a respiratory stimulant in various forms of narcosis was first 
demonstrated in the laboratory by H. C. Wood, and subsequently cases were reported by Clara 
Dercum (U. M. M ., 1870) and others. 

In regard to the value of atropine, E. F. Bashford {A. J. P., 1901, viii.) confirms its usefulness 
in opium-poisoning; while in a very elaborate paper E. T. Reichert {T. M ., 1901) reaches the 
conclusion that very frequently the overdosing of cases of morphine-poisoning with atropine has 
contributed to the fatal result, and that it is only of use as a respiratory and stimulating agent 
before the third stage of the poisoning is reached; and further, that, on account of its in many 
ways synergizing with morphine, it is dangerous when given in overdose. In these conclusions 
Reichert seems to us correct. 

For cases in which cocaine was used in opium-poisoning, see Amer. Med. Journ., 1901. 



70 GENERAL REMEDIES 

end of the Becond long stage, bo as to get its stimulating influence 
upon the heart in the coming depression. 

As the result of numerous experiments, E. T. Reichert reaches 
the conclusion that cocaine is almost completely antagonistic to 
morphine, combating the influence of the morphine not only upon 
respiration and circulation, but also upon the general metabolism, 
and synergizing with the morphine only in its action upon the spinal 
cord.' He finds that, on the whole, it acts more powerfully upon 
morphinized than upon normal dogs. 

In bad cases of opium-poisoning the use of artificial respiration 
should not be postponed. In some cases the Sylvester method may 
suffice, but, as was first shown by Fell, forced respiration (see page 
48) should be resorted to whenever respiration fails. Fell has re- 
ported recovery obtained in this way after the ingestion of thirty- 
three grains of morphine. So long as any movement of the heart 
continues, the forced respiration should be steadily maintained. 
Inhalations of oxygen apparently saved life in a case reported by 
Playfair. In some cases the lungs become filled with bronchial 
mucus; under such circumstances good may be achieved by placing 
the patient in an inverted position. It is often essential to keep up 
the temperature of the body by artificial means. Lauder Brunton 
and Cash have found that the fall of temperature in the poisoned 
mammal is not prevented by placing the animal in a temperature 
a little below that of the body, and the ordinary methods used in the 
sickroom to heat the cooling human body are of very little service. 
The hot bath or a water bed, two-thirds filled with water of the tem- 
perature of 150° F., may be employed. The subcutaneous or intra- 
venous injection of normal saline solution has proven of value in 
desperate cases; the solution probably aids in the elimination of 
the poison and the maintenance of the circulation. 

Opium-poisoning usually has no sequela?, but amaurosis and 
glycosuria have been reported. 

In regard to the amount of opium which will cause death, the 
smallest fatal dose in the adult on record is one-sixth of a grain of 
morphine.* According to A. Calkins, four grainsf of crude opium 
placed in the ear have caused death; also four grains by the mouth 
in more than one case. According to the authority just quoted, out 
of twenty-nine reported cases in which a fluidounce of laudanum 
was taken, nine died. The maximum doses from which recovery 
has occurred without emesis are fifty-five grains of the solid opium 
and six ounces of laudanum. The death of an adult female has been 
attributed, with doubtful accuracy, to thirty grains of Dover's powder, 
given in divided doses. Recovery is asserted after eighteen grains 
of morphine without vomiting (William C. Chaffee), thirty grains 
with vomiting (Playfair), and even thirty-three grains (Fell). 

* A number of cases are on record in which death has been produced in the adult by the 
hypodermic use of from one-sixth to one-half grain of morphine. Consult Chicago Med. Examiner, 
May, 1878; Quart. Journ. Psycholog. Med., 1868, ii. 739; also Bos/. Med. and Surg. Journ., 1885, i. 

t Taken from the Journal de Chimie, 1831. Assuredly there is a mistake in this case. 



SOMNIFACIENTS 71 

Morphine Habit. For full details as to the results of the habitual 
use of opium or its alkaloid, the reader is referred to the treatise of 
Albrechl Erlenmeyer {Die Morphiumsucht). No confidence can be 

placed in the statements of the opium-cater, and it is essential for 
cure that such person be in a hospital or be confined to an apart- 
ment under the care of an absolutely reliable nurse, so that the orders 
of the physician can be strictly enforced. The basis of the treatment 
must consist in the withdrawal of the narcotic, and there are three 
distinct ways in which this can be effected. First, the opium may 
be suddenly taken away; secondly, it may be taken away rapidly, 
but not suddenly; thirdly, it may be withdrawn very gradually. 
The first of these methods is undoubtedly in most cases efficient, 
but is often attended by grave danger of collapse, and has no distinct 
advantages over the plan of rapid withdrawal. The time required 
for the very gradual withdrawal of the remedy is too great for prac- 
tical purposes, and the sufferings of the patient are too long drawn 
out. Unless the daily dose has been extraordinary or the patient is 
in a very feeble condition, it is safe to withdraw the narcotic entirely 
in from seven to twelve days. A convenient plan is to direct that a 
solution of morphine or opium be prepared, and whenever a dose 
is taken out an equivalent amount of water be added. The chief 
symptoms that follow the rapid withdrawal are excessive malaise, 
insomnia, complete loss of appetite, vomiting, diarrhoea, and great 
feebleness. We have never yet seen a case in which these symptoms 
were so uncontrollable as really to cause alarm for the safety of the 
patient. Much may be done by proper feeding. The food should 
consist of highly nutritious, stimulating, and easily digested articles, 
and in severe cases should be liquid, such as milk, rich soups, etc. 
When the circulation fails, alcohol may be used, and much relief 
may be afforded by massage, and often by simple rubbing of the 
patient. General electrical stimulation and faradization of the 
muscles is often useful, not only by its effect upon the circulation, 
but also by distracting the attention of the patient from his sufferings. 
The use of the alkaloid cocaine as a stimulant has been recommended. 
Good results may be obtained from the free internal administration 
of the fluidextract of coca, but the use of hypodermic injections of 
cocaine seems hardly justifiable, as the danger of setting up the 
cocaine habit is too great. If gastro-intestinal irritation exists, 
bismuth may be administered freely. The diarrhoea is usually con- 
trollable by' mild vegetable astringents, especially if combined with 
sulphuric acid. If the bodily temperature falls at all, it must be 
maintained by external warmth. Potassium bromide, ammonium 
valerate, compound spirit of ether, and other similar feeble nerve- 
sedatives may be employed and give some comfort. Moral support 
and stimulation are essential, and massage or other device which 
aids in passing the time of suffering is most beneficial. 

Opium- Smoking. — The various nations of the Orient use opium 
as an intoxicant by smoking in one of two ways. In Turkey and 



72 GENERAL REMEDIES 

neighboring countries it is placed upon tobacco, in a small pipe. 
In the East it is usually made into a thick, almost plastic, liquid, a 
large drop or ball of which is held over the flame of a small oil lamp, 
and the resulting fumes inhaled through pipes of various forms. 
For an elaborate study of the chemistry of the opiums used in various 
countries, see Apotheker Zeitung, 1903. 

.Moissan has found in the smoke of opium: morphine, pyrrol, 
pyridine and various homologues, acetone, and various hydropyri- 
dine bases, all of which are physiologically active. This analysis 
has been confirmed by Hartwich and Simon, who believe that the 
activity of the opium smoke depends not so much upon the morphine 
as upon the other products of the destructive distillation. 

Codeine. — According to the statements of various observers, 
codeine produces, in the lower animals, symptoms very similar to 
those caused by morphine, — namely, in the frog, heightened reflexes, 
tetanic cramp with convulsions, also coma; in the pigeon, restless- 
ness, disturbances of respiration, violent convulsions; in the dog, 
disturbances of respiration, languor, convulsive twitchings, also sleep. 
For detailed discussion of the observations of various investigators, 
see tenth edition of this work. 

In man codeine is a very uncertain and feeble hypnotic, whose 
action, especially after large doses, is sometimes attended by marked 
restlessness. The statements of various clinicians as to its effects 
and practical value vary veiy greatly, the variance probably depend- 
ing largely upon the quality of the codeine used, in many cases the 
drug exhibited having in all probability been contaminated with 
morphine. In S. Weir Mitchell's experiments upon himself five 
grains produced no symptoms except slight increase in the pulse- 
rate, nausea, some giddiness, and a sense of heaviness about the 
head; results which are in accord with the earlier experiments of 
Harley. Contrariwise, A. S. Myrtle records a case of severe poisoning 
caused by four grains of codeine. There was first vascular excite- 
ment and exhilaration, then depression with great anxiety, nau- 
sea and vomiting, pale, cool, clammy skin, slight contraction of 
pupil, and sleeplessness, with slight delirium. Two cases of serious 
poisoning by eight grains have been reported.* 

In our experience codeine has proved to be a practically useless 
remedy except for the purpose of controlling bronchial irritation in 
phthisis and other diseases. 

In former editions of this treatise the non-official opium alkaloids narceine, 
narcotine, thebaine, papaverine, laudanine, porphyroxine, anarcotine, and crypto- 
pine were discussed at length, but, as they have failed entirely to come into use as 
therapeutic agents, their consideration is here omitted: a full summary of our 
knowledge of their physiological action may be found in the tenth edition of this 
work. 

* See Brit. Med. Journ.. 18S8, ii., and New York Med. Record. 1893, xliv. 



SOMNIFACIENTS 73 



MORPHINE DERIVATIVES. 

Various derivatives of the alkaloid morphine are physiologically 
active, but only two of them are at present used, Peronine (mor- 
phine benzylester hydrochloride), an account of which may be found 
in the eleventh edition of this book, having fallen into complete 
desuetude. 

DlONINE (monoethylester of morphine hydrochloride) is a white 
crystalline powder, soluble in seven parts of water. Although no 
careful physiological research has been made upon it, it appears to 
share to a slight extent the analgesic and hypnotic powers of mor- 
phine, and not ordinarily to produce nausea, constipation, or other 
disagreeable after-effects. It is affirmed to be more active than 
morphine in the suppression of cough, and to be also actively anti- 
hydrotic, so that it is of especial value in advanced pulmonary 
tuberculosis. It ha*s also been commended in asthma and as an 
anaphrodisiac; also in dysmenorrhea. The dose is from one-quarter 
to one-half grain (0.015-0.03 Gm.) in powder, pill, or solution. The 
general professional verdict seems to be that, on the whole, it 
resembles heroine in its therapeutic value, but is less powerful. 

Ophthalmic Uses* — As first noted by Wolffberg, one drop of a two-per-cent. 
solution of dionine placed upon the conjunctiva immediately produces smarting 
and burning pain free lachrymation, marked injection of the conjunctival blood- 
vessels, chemosis of the conjunctiva, and occasionally swelling of the lid. This 
"dionine reaction'' varies very much; sometimes it almost fails to appear. Under 
these circumstances a stronger solution, for example, five to ten per cent., will 
usually avaih or, according to Darier, an even more active effect may be produced 
if a morsel of powdered dionine is used, or if the solution is injected beneath the 
conjunctiva. The irritative effects of the drug are at times exceedingly violent, 
and Darier believes that the oedema of the conjunctiva, and, moreover, one that 
spreads to the lids and tissues of the face, is more pronounced in the subjects of 
vascular disease, nephritis and scrofula. The dionine reaction takes place in the 
normal as well as in the diseased eye. Usually it subsides materially within an 
hour. It may continue for a number of hours, although the pain and smarting 
almost always disappear in a very short space of time, to be followed by a period 
of analgesia lasting for several hours. 

The phenomena of dionine reaction have been aptly described by Wolffberg 
by the term "lymphatic inundation," and Darier, who is particularly enthusiastic 
in his recommendation of the value of this medicament, thinks that lymphatic 
inundation washes out not only the surface of the eyeball but also the subcon- 
junctival and intracorneal lymph-spaces, and perhaps even the intraocular spaces. 
There is, according to this author, not only an afflux of liquid but also of lympho- 
cytes, whose duty he believes is concerned with the defence of the parts, so that 
there is a more active production of antitoxins and phagocytes. Whether the drug 
really has an action upon the diseased processes of the eye themselves and aids its 
resolvent power by a subtraction of pathologic fluid, or whether its influence should 
be regarded as that of a counter-irritant, or whether it depends upon its power of 
increasing lymphatosis, has not been decided, and at present it is probably not 
possible to say that it does more than stimulate the lymphatic and vascular cir- 
culation of the eye. So far as I am aware, the only untoward recorded result from 

* This account of the local action of dionine was written by Prof. George E. de Schweinitz. 



71 GENERAL REMEDIES 

its action is one case of macular hemorrhage in practice. Violence of reaction 
without ultimate bad results is not an uncommon phenomenon. 

[ta indications in ophthalmic therapeutics are numerous, and in general terms 
it may be stated that it has a favorable influence in alleviating painful inflamma- 
tions of the anterior portion of the eye, and in relieving the distress incident to 
increased intraocular tension, that is, glaucoma. There is much evidence to show 
that it facilitates the absorption of atropine, eserine, pilocarpine, etc. It is useful 
in iritis, irido-cyclitis, simple and infected corneal ulcers, herpes of the cornea, super- 
ficial and parenchymatous keratitis, and in the various types of glaucoma. There is 
some evidence that it is of value in deeper inflammatory processes, for example, 
in uveitis, and it certainly relieves post-operative inflammation and infection. It 
would seem, according to an observation of Dr. Callan, which I think I can confirm 
from personal experience, that it facilitates the regeneration of corneal tissue. It 
may be suitably combined with cocaine, atropine, eserine or pilocarpine where 
these drugs are also indicated; but I believe that a better result is reached if the 
dionine is used separately, and the atropine, cocaine, etc., is instilled immediately 
afterwards. In a very brief time, usually after the third or fourth day of its use, 
the eye establishes a species of immunity, and the dionine reaction almost fails to 
appear. Therefore, it should be used for two or three days, and then omitted for 
three days, when again the reaction is likely to appear; or, if it does not appear, 
the strength of the solution may be increased. 

It is the practice of some surgeons, following Darier's recommendation, to use 
a five-per-cent. solution. If, however, this occasions too much reaction, in my 
own experience a one-pcr-cent. solution acts favorably, and I have almost abandoned 
the employment of the stronger preparations, except when a very decided reaction 
is desirable, or when immunity has been secured. Instead of employing dionine in 
solution, it may be used in powder, for example, a twelfth of a grain (0.005 Gm.), 
or the powder may be dusted directly upon an ulcerated surface. With this method 
of employment, recommended by Darier, I have had little experience. I have also 
not prescribed it as a salve, although this method of employment has been advised 
and commended by others. Darier has used it subconjunctivally, combining it 
with a physiological salt solution under these circumstances, by injection. The 
reaction is very violent; but, for example, in detachment of the retina, is said to be 
of service. 

The asserted power of dionine of clearing up corneal scars I believe to be doubt- 
ful, but it certainly is effective and very useful in certain interstitial deposits, such 
as those of interstitial keratitis, both in the early and in the late stages of the disease. 
The solutions should be freshly prepared to be of service. 

Heroine (diacetyl ester of morphine), which occurs as a colorless, 
odorless, bitterish crystalline powder, is nearly insoluble in water, 
but forms a hydrochloride which is freely soluble both in water and 
in alcohol. According to Dreser, confirmed by Strube, it produces 
in the lower animals stupor with convulsions, but has very little 
influence upon the circulation. Ott has found that in the frog it 
lessens reflex activity, and in sufficient doses causes complete paraly- 
sis which is independent of any effect upon the motor nerve or muscle. 

All observers are in accord that it has very little action on the 
circulation. According to Ott, in doses of from one-twentieth to 
one-tenth of a grain it produces in the rabbit slight elevation of the 
pressure without much change in the pulse-rate. The dominant 
action of heroine. is upon the respiratory centre. Impens, Marshall 
and Fonteyne state that in small doses it slows the rate but slightly 
increases the depth of the respiration, while in large amounts it 
lessens both the frequency and the depth. According to Impens, heroine 



SOMNIFACIENTS 75 

does not diminish the irritability of the respiratory centre towards 
carbonic acid, as do both morphine and codeine; this statement is, 
however, in direct conflict with Dreser. 

From the experiments of Impens and Mayor there can be little 
room for doubt that, at least as regards the lower animals, it requires 
less heroine to kill than it does morphine. It is probable that this 
statement holds true also for the human being. As has been pointed 
out, however, by Impens and by Morel-Lavallee, heroine is a less 
dangerous drug than morphine, because the efficient dose is dispro- 
portionately smaller than the fatal dose in comparison to morphine. 
In other words, although it requires about half the quantity of heroine 
that it does of morphine to kill, it requires only about one-fourth 
of the quantity to exercise its maximum sedative effect upon the 
respiratory centre. 

Toxic symptoms following the use of heroine are uncommon. Two and a half 
grains are said to have produced in an asthmatic adult syncope, myosis, blindness, 
and subnormal temperature, lasting for many hours, and Dover reports great pros- 
tration, dilated pupils, with mental aberration, produced by three grains. Thompson 
reports death in a case of severe mitral disease, which he attributed to heroine. In 
a few instances nausea and vomiting have followed the use of heroine, perhaps due, 
as claimed by Robinson, to some chemical change in the drug. In a number of 
cases heroine has caused constipation. 

As an hypnotic or analgesic heroine is certainly very much inferior 
to morphine, but it has the advantage that in chronic cases it does 
not produce the agreeable sensations which render the latter drug so 
dangerous. In arresting cough it has seemed, in our experience at 
least, equal to morphine in activity, and has the great advantage of 
not checking secretion either in the lungs themselves or in the ali- 
mentary canal. According to Strauss, it has distinct anaphrodisiac 
properties, making it useful in various forms of sexual excitement, 
such as nymphomania and masturbation. It has been recently as- 
serted, especially by E. Elischer, that it is so active as a local anal- 
gesic that one-quarter of a grain introduced into the vagina will 
relieve the suffering even of uterine cancer. Rosenberg commends 
a two and a half grains to the fiuidounce solution as a local anesthetic 
in diseases of the throat, and especially in laryngeal tuberculosis. 
When there is excessive cough, as in asthma, bronchitis, and whooping- 
cough, heroine is a very valuable drug; in phthisis it has the further 
virtue of reducing the tendency to sweating. Dose, from one-tenth 
to one-third of a grain (0.006-0.02 Gm.). The hydrochloride may be 
used hypodermically. 

HYDRATED CHLORAL. 

Chloral, or trichloraldehyde (C 2 HC1 3 0), which is itself not used 
in medicine, is an oily liquid giving off, at the ordinary temperature, 
pungent fumes, made by the action of chlorine on alcohol. It 
unites with one molecule of water to form a hydrate. 



76 GENERAL REMEDIES 

Hydrated Chloral is a volatile, crystalline solid, of a hot, burning 
taste, freely soluble in water, ether, and alcohol. It usually occurs 
as transparent, colorless tablets, but sometimes in acicular or even 
in rhomboidal crystals. If an alkali be added to a solution of 
hydrated chloral, it breaks up into formic acid and chloroform. 

Chloralum Hydratum 10 to 20 grains (0.6-1.3 Gm.). 

Local Action. — Hydrated chloral is distinctly germicidal and 
antiseptic, and was at one time used to some extent for preserving 
cadavers, keeping urinals pure, and allied purposes. As shown by 
Keen, a solution of twenty to forty grains to the ounce will preserve 
animal tissues almost indefinitely without interfering with their 
microscopic structure. It is also somewhat irritant in its action, 
and after a time sedative to the sensory nerves, and, it may be, to 
all tissues. 

Absorption and Elimination. — Hydrated chloral is absorbed with 
great rapidity, its action being often manifested within five minutes 
after its ingestion. It circulates through the body as chloral; its 
exact fate in the system has not been determined, but it probably 
escapes from the body in part unchanged and in part in the form of 
compounds. It was recognized in the urine by A. Tomascewicz by 
means of the delicate isocyanphenol reaction* of Hoffmann. Feltz 
and Ritter found in the urine of chloralized animals, a copper reducing 
substance which Von Mering and Musculus have separated, as uro- 
chloralic acid, in colorless, shining needles, often arranged in star- 
like groups, soluble in water and in alcohol, insoluble in ether. The 
existence of this acid has been confirmed and its chemical proper- 
ties studied by A. Borntraeger and by E. Kulz, who found it to be 
physiologically inert. 

Physiological Action. — Nervous System. — The most constant 
and prominent of all the sj^mptoms produced by moderate doses of 
hydrated chloral is sleep, due to a direct depressant action upon the 
higher cerebral centres. The drug seems also to affect the psycho- 
motor area but sensation is not affected except after toxic doses. 
Generally, as already stated, the sleep is quiet, but sometimes it is rest- 
less, and in man has occasionally even been wildly delirious, although 
it is somewhat uncerta'n whether the latter condition may not have 
been due to impurities in the drug. It seems to be well established 
that in the milder degrees of this sleep there is no anesthesia. We 
have seen the hyperesthesia! spoken of by Demarquay after small 
doses of chloral, and there can be no doubt that it is an occasional, 
if not a constant, phenomenon. Rajewsky states that there is in 
frogs a corresponding period of over-excitability of the reflex centres, 

* Many chemists have failed to find chloral for want of a delicate test. F. Ogston (Edin. 
Med. and Surg. Journ., xxiv. 292) affirms that ammonium sulphide affords a means of recognizing 
minute amounts of the drug. 

t Bouchut (New York Med. Gazette, Dec. 1870), Dieulafoy and Krishaber (Amer. Journ. 
Med. Sci., Jan. 1870), Giovanni and Ranzoli (Schmidt's Jahrbiuher, cli.), and Rajewsky (Ibid.) 
confirm this, while l.iebreich and Labbde deny it; riammarsten, who has noticed such hyper- 
esthesia, is inclined to think it apparent rather than real. 



SOMNIFACMKNTS 



77 



and that in rabbits he has noticed a glowing heat borne without 
much complaint, when pinching would produce violent outcries. 
In very large doxvx chloral produces anesthesia ; but, unless the amount 
employed be so great as to be toxic, this anesthesia is in most cases 
very trifling. 

The paralysis and loss of reflex excitability induced by chloral 
are spinal in origin and are not due to any action on either peripheral 
nerves or muscle. 

Labbee has shown that the muscles respond to electrical stimulation of the 
nerve and also directly of the muscles, even after fatal doses. The experiments 
of Rajewsky has continued the retention of irritability of the motor-nerve and has 
also found that in the latter stages of chloral-poisoning direct irritation of the spinal 
cord gave rise to much less severe spasms than in the unpoisoned animal. Before 
this paralytic stage is reached, as already stated, Rajewsky affirms that in the frog 
there is a period of increased reflex activity, and that at this time stimulation of 
tin- spinal ganglia shows that they are more susceptible than normal. The observer 
last named states that these phenomena occur just as freely after destruction of 
Setschenow's centre in the frog as before, and are therefore independent of it. 

Circulation. — The administration of hydrated chloral in any dose 
large enough to affect the circulation produces a fall of blood-pres- 
sure with usually slowing of the pulse-rate. The fall of the blood- 
pressure is due largely to a depressant action on the heart although 
after large doses there is also complete paralysis of the vaso-motor 
mechanism. 

In man, Bouchut and Anstie and Andrews obtained sphygmographic traces 
which they think indicate a primary increased arterial tension, but Nancias, of 
Venice, has found the tension normal. Preisendorfer, in a series of sphygmographic 
studies, thought that there might be a brief primary rise of arterial pressure in man, 
as in animals, but under the full action of chloral the arterial pressure steadily sinks. 
We do not think that much confidence is to be attached to these observations, since 
the sphygmograph seems to be an entirely unreliable instrument when used for 
the comparative study of arterial pressure. Both Rajewsky and David Cerna have 
found that chloral, in whatever dose, produces no rise in pressure but always, if 
the quantity given is sufficient, a lowering, so that if any rise of pressure (as seems 
improbable) is ever produced in the normal man or animal by chloral, such rise 
must be indirect and, probably, due to respiratory disturbance. The fall of blood- 
pressure is probably owing in part to the vaso-motor paralysis, but perhaps in 
largest part to depression of the heart. The vaso-motor palsy is probably chiefly 
caused by an action upon the dominant centre, but Kobert has shown that there 
is also, after a very large dose of the chloral, palsy of the coats of the vessels. 

The lessening of the pulse-rate Cerna believes to be due to an influence upon 
the cardio-inhibitory centres, but Rajewsky asserts that the slowing occurs in the 
fro" and rabbit after section of the pneumogastric nerves and is, therefore, not 
due to central inhibition. When toxic doses have been employed, the heart, after 
numerous pauses, is finally arrested in diastole. Analogy indicates very strongly 
that this arrest is due to a direct influence upon the heart-muscle or ganglia, and 
the researches of Sidney Ringer and H. Sainsbury and of David Cerna seem to 
demonstrate (the contrary results obtained by Labbee notwithstanding) that 
when chloral is brought in direct contact with the isolated heart of the frog there is 
an immediate and persistent loss of power, ending finally in diastolic arrest. In 
poisoning in man, the pulse has towards the last been very feeble, generally rapid 
and irregular, and even in some cases in which recovery has occurred it has been 
altogether absent for a time. 



78 GENERAL REMEDIES 

Respiration.— In full doses, chloral lessens the number of respira- 
tions per minute, causing them to become slow and full; when toxic 
doses arc taken this action becomes more and more marked, the 
rhythm is much affected, and the respiration grows markedly irregu- 
lar, and sometimes very rapid and shallow, until it ceases. As these 
phenomena occur equally after section of the vagi (Rajewsky), the 
influence of chloral must be exerted upon the respiratory centre. 

Tissue Change. — Charles Richet has found that toxic doses of 
hydrated chloral reduce very greatly the elimination of carbonic 
acid, at the same time that they lower the bodily temperature. So 
far as large doses are concerned, A. Gritzka is in accord with this, 
although he asserts that small doses increase carbonic acid elimina- 
tion. It is plain that the profound muscular quiet produced by chloral 
must lead to lessened oxidation. Julius Peiser affirms that chloral 
increases the degeneration of albuminous tissues. 

Abdominal Action. — Clinically hydrated chloral has no perceptible 
action upon the gastro-intestinal mucous membrane, save as a local 
irritant; but, according to the experiments of Wertheimer and Le- 
page and of Charles Dubois, it increases in the animals both pan- 
creatic and biliary secretion, chiefly, but not altogether, as the result 
of its local influence in the duodenum and jejunum. 

Temperature. — A most remarkable action of hydrated chloral is 
upon the temperature: in this point all observers are in accord with 
Richardson, of London, who has seen the temperature fall 6° F. in a 
rabbit which recovered. Bouchut has noticed a fall of 2° (C. ?) in an 
infant, and Da Costa and other observers have noticed slighter 
reductions of temperature in man after therapeutic doses. In a case 
reported by Levinstein, after six drachms of hydrated chloral the 
temperature rose to 39.5° C. (102.1° F.), and subsequently fell to 
32.9° C. (91.22° F.). Hammarsten has found that the fall of tem- 
perature is very rapid, 6° C. in an hour, and that it occurs in animals 
well wrapped up and laid in a warm place. 

SUMMARY. — Upon the cerebrum hydrated chloral acts as a 
powerful hypnotic; in full doses it acts as a depressant upon the 
centres at the base of the brain and upon the spinal cord: it 
causes slowing and weakness of the heart's action, and probably 
vaso-motor paralysis, also centric slowing of the respiration, with 
loss of reflex activity, muscular weakness, and some anesthesia, 
all of spinal origin; in fatal doses it usually produces a gradual 
death by paralyzing the respiratory centres in the medulla, al- 
though in rare cases it kills suddenly by directly paralyzing the 
heart, which always stops in diastole. On the vagi and on the 
motor nerve-trunks it has no marked influence. 

Action as Chloral. — Liebreich was led to the discovery of the value of chloral 
as a practical medicine by the knowledge of the fact that it is converted when in 
solution by alkalies into chloroform and formic acid, and the expectation tnat 
chloroform would be generated by the alkalinity of the blood. This theory, which 
:il one time held, has been so completely disproved as almost to have been lost 
sight of. A discussion of it may be found in full in the tenth edition of this treatise. 



SOMNIFACIENTS 79 

Therapeutics. — The results of the clinical use of hydrated 
chloral are in strict accord with its known physiological action. The 
indication which it most usefully meets is to induce sleep. The more 
purely nervous the wakefulness the more successful the remedy. 
When from functional over-excitement of the brain due to excessive 
mental strain, or from anxiety or other kindred cause, the patient 
cannot sleep, hydrated chloral is, probably, the most certain of the 
hypnotics. On the other hand, when severe pain causes wakefulness, 
it is of very little value, — at least in doses which we think safe. Some- 
times even in these cases sleep will come, but it will very often be a 
restless, troubled sleep, with moaning or other indications of suffer- 
ing; and it may be that the patient on awaking will complain that 
he has suffered more while sleeping than when awake. 

In the sleeplessness occurring at times during convalescence from 
acute disease chloral is very efficacious. In the early stages of fevers 
it is sometimes of advantage; Russell recommends it especially in 
the wild delirium of typhus in its earlier stages. In advanced fever- 
cases, when the symptoms are gravely adynamic, we believe that 
the use of chloral would be very perilous. In delirium tremens it 
often induces sleep readily, but not rarely it fails, even in large dose. 
In the sleeplessness of acute puerperal or non-puerperal mania there 
is abundant testimony to the value of chloral. It must not be for- 
gotten that chloral is a dangerous remedy when there is cardiac 
weakness; and when in any of the diseases just spoken of there is 
reason to suspect a fatty or even a feeble heart, great care must be 
exercised in its administration. Under such circumstances the dose 
of fifteen grains (1 Gm.) should not be exceeded, and should not be 
repeated more than once unless after an interval of several hours. 

The second indication to meet which hydrated chloral may be 
employed is to relax spasm. For this purpose it has been used with 
advantage in puerperal and uremic convulsions. It must be remem- 
bered that in many of these cases, although next to chloroform the 
best palliative, it is only a palliative, and must be used merely to 
quiet the nervous disturbance until other remedies can have time to 
act. In tetanus it is one of the most valuable agents we have for 
controlling the convulsions, but it must be given boldly and at short 
intervals. Extraordinary results have been obtained by Macna- 
mara in tetanus by using hydrated chloral simply at bedtime (forty 
grains), with an occasional dose (thirty grains) in the morning when 
there is high temperature; and administering brandy, milk, and 
eggs very freely during the day. 

In trismus nascentium, as originally recommended by Widenhofer, 
it is undoubtedly very valuable. Widenhofer gave it to the young 
babe in one-and two-grain doses by the mouth, or, when the spasms 
prevented, in double the quantity by the rectum. In chorea it is not 
directly curative, but is of great importance when it is essential to 
temporarily check the violence of the movements. As a nocturnal 
quietant and hypnotic, it is of the highest value in cases of acute 



80 GENERAL REMEDIES 

chorea in which speedy death is threatened from the incessant and 
violent movements; also in cases complicated with fractures, where 
a temporary lull is of importance. In puerperal convulsions its use 
in large doses has met with a great deal of favor. A half-drachm 
may be exhibited at once, and half the quantity every hour or two 
pro re nata. 

In the convulsions of children it has been employed with apparent 
good; in cramps, in singultus, in the spasmodic nocturnal enuresis of 
children, in laryngismus stridulus and other spasmodic affections of 
the glottis, in nocturnal emissions, in whooping-cough, and in all forms 
of severe spasmodic disorder when it is desired temporarily to sup- 
press the motor disturbance, chloral remains the standard remedy. 
In asthma it has sometimes been of use, but more often it has failed. 
Its hypodermic use in the algid stage of cholera, as recommended by 
Dr. Hall, appears to us of very doubtful value. 

The third indication for which chloral has been used is to relieve 
pain. That it will do so when given in very large doses there can be 
no doubt; but, unless the dose be so large as to be dangerous, it is 
of little value as an analgesic. Its powers in this direction are incom- 
parably less than those of opium, and its habitual use is attended 
by grave dangers. 

As originally suggested by Lyon Playfair, hydrated chloral may 
be given in the early stages of labor to lessen the severity of the pain; 
it is stated also to be of service as a relaxant when there is rigidity 
of the os. Fifteen grains may be administered and repeated in half 
an hour if necessary. 

Locally a solution of chloral (ten per cent, to saturation) has 
been used with asserted very good effects as a stimulant and anti- 
septic in foul ulcers, buboes, bedsores, etc., especially when the dis- 
charge is free, — as a hemostatic when there is oozing of blood, — 
and as an antiseptic and local anesthetic in uterine and other cancers. 
Applied to the skin, it is a powerful irritant, and has been proposed 
as a vesicant,* but is said to cause excessive pain. 

The intravenous injection of chloral, as suggested by Ore, for 
the purposes of anesthesia, and for the combating of tetanic spasms, is 
entirely unjustifiable and is at present rarely practised, death having 
in various cases resulted from the unexpected violence of its action 
or from the coagulation of the blood which is produced. 

Administration. — Although the continuous use of hydrated 
chloral may lead to a very serious chronic poisoning, we have no 
knowledge that the chloral itself accumulates largely in the system. 
On the other hand, the single large dose of hydrated chloral in rare 
cases acts with unexpected violence, and it should, therefore, never be 
given in doses of over twenty grains, and this amount should not be 

* According to Bonnet (Union Phorm., xlii. 490), one gramme of hydrated chloral rubbed up 
with oil of sweet almonds or vaseline and spread on a diachylon plaster twelve by fifteen centi- 
metres and placed on the skin, will in fifteen minutes cause burning pain, after which time it should 
be removed and the part covered with cotton wool. During the sleep, which usually follows the 
absorption of the chloral, a blister will form. 



SOMNIFACIENTS 81 

repeated oftener than once an hour, and, when sixty grains have been 
taken, not again for some hours, unless in very urgent cases, as acute 
tetanus or violent chorea threatening speedy dissolution. 

Reynolds reports a case in which forty-five grains caused most alarming symp- 
toms and H. W. Fuller a number of cases in some of which very alarming symptoms 
followed the exhibition of thirty grains, and in one, death in a healthy young woman 
of thirty. Schwaighofer, of Vienna, records coma and death in a drunkard follow- 
ing the ingestion of half a drachm. W. H. Lathrop details the case of a man pre- 
viously healthy, but suffering from delirium tremens, who took sixty grains between 
12 and 1 p.m., at 2.30 p.m. twenty grains more, and at 3 p.m., no effect being mani- 
fest, twenty grains more. His physicians then left him sleepless and complaining 
only of a slight paralysis of the lower extremities; and almost in a moment he was 
dead. Other cases might be quoted, but the above are sufficient to show that chloral 
may kill suddenly and unexpectedly. 

An observation of Vulpian throws much light upon these sudden deaths. He 
found that galvanization of a divided vagus would cause in a chloralized animal 
not momentary, but permanent, arrest of respiration, if the centric end was selected, 
or permanent diastole of the heart if the distal part of the nerve was attacked. 
It is very probable that in a man under the influence of chloroform or of chloral, 
death may be precipitated by a slight peripheral inhibitory irritation. 

Toxicology. — The earliest symptoms of hydrated chloral- 
poisoning is sleep, which in mild cases closely resembles natural 
sleep. The subject can readily be aroused from the lighter degrees 
of this, waking to full consciousness, but soon dropping off again 
when left quiet. The pulse is in this degree of action not affected, 
or is rendered a little slower; the pupil is contracted, but becomes 
normal so soon as the subject is awakened; the respiration is 
deep, full, and regular. When larger amounts are given, the sleep 
is much deeper, and may pass into profound coma; the respirations 
fall in number; the pulse at first is weakened and rendered slower, 
but later may become rapid and irregular; the temperature is re- 
duced; the muscular system is relaxed, and both sensibility and 
reflex action are diminished. If a fatal dose has been taken, all these 
symptoms are intensified; with coma, intense muscular relaxation, 
weak, thready pulse, and a pupil contracted at first, but afterwards 
dilated, the victim gradually sinks into death, paralyzed and anes- 
thetic. The immediate cause of death is usually a centric paralytic 
arrest of respiration; but in many cases there appears to be a simul- 
taneous arrest of the cardiac action, and it is probable that fatal 
syncope may at times occur. 

The minimum fatal dose of hydrated chloral is hardly established, 
but thirty grains have produced death. (See Administration.) In 
very many cases, however, recovery has occurred after the taking 
of several drachms; indeed, Eshleman has reported recovery after 
the ingestion of four hundred and sixty grains. There are no pathog- 
nomonic lesions found after death from chloral, but a dark, bloated 
countenance and other evidences of death from asphyxia have been 
noted; congestion of the meninges and substance of the brain and 
cord, and of the lungs, is commonly found. The blood is thought 
by Richardson to coagulate less firmly than when normal. 
6 



82 GENERAL REMEDIES 

There is no satisfactory chemical antidote to chloral. The treat- 
ment is in general similar to that of opium-poisoning, consisting in 
the free use of internal and external stimulants, such as sinapisms, 
dry heat, frictions, flagellations, etc., to maintain the circulation, 
and of shaking, application of the dry electric brush, cold douches, 
etc., to keep up the respiration. In practising these measures it 
must be remembered, however, that the patient in chloral-poisoning 
is much more likely to die of exhaustion, and especially of cardiac 
failure, than in opium-poisoning, and that therefore those methods 
of arousing the nerve-centres which do not, like walking, require the 
expenditure of effort on the part of the patient are to be preferred. 
Artificial respiration should always be resorted to before natural 
respiration altogether fails, and Clemens has found that animals 
asphyxiated by chloral may often be at once aroused by the inhala- 
tion of oxygen. Atropine and strychnine are important remedies. 
B. W. Stone reports recovery from four hundred and twenty-five 
grains of chloral after the hypodermic use of one-fifth of a grain of 
strychnine in divided doses. Digitalis may be given to sustain the 
heart. I. M. Booth reports a case of recovery after about one hun- 
dred and ten grains of chloral under the use of tincture of belladonna. 
Lauder Brunton has shown that if the bodily temperature be main- 
tained artificially animals survive doses of chloral usually fatal, and 
in human chloral-poisoning the bodily warmth should be maintained 
by the use of dry external heat, hot blankets, hot baths, and other 
devices. 

While some affections have been erroneously attributed to chronic 
chloral-poisoning, there seems to be no doubt that its long-continued 
use often does produce serious symptoms. 

The cases are divisible into two or three groups, which are, however, really 
artificial, as is shown by the occurrence of cases belonging to two or even three of 
the groups. In the first group the respiration is chiefly affected. The dyspnoea may 
be slight, and may be felt at times, as after exertion or after meals; but it may be 
constant and alarming. Cases of this character are reported by Jastrowitz, by 
Schule, and by Ludwig Kirn. In one instance (N. R. Smith), death from bronchial 
effusion is believed to have been caused by chloral. Kirn affirms that in some cases 
mental disturbance with hallucinations occurs. 

In the second group of cases, eruptions of the skin are the chief manifestations 
of the toxemia. These vary in intensity from the occasional appearance of tran- 
sient red blotches on the face or neck to an intense, even livid, erythematous red- 
ness of the face. In other instances there is marked erythema (Schule), occurring 
first in spots upon the face, but extending downward to the trunk, becoming more 
and more general, and showing a marked tendency to follow the nerve-trunks. 
This erythema is seemingly due to vaso-motor weakness, and consequently is allied 
to other more urgent symptoms seen in chloral toxemia. Sometimes it invades 
the mucous membranes, which become red, swollen, and oedematous; and if the 
glands are involved, as in a case reported by Chapman, the result may be serious. 
A deeper implication of the vaso-motor and cardiac nervous system was prob- 
ably the cause of the general oedema, profound weakness, and failure of heart- 
action in the case recorded by N. R. Smith and possibly also of the desquamation 
of the cuticle and ulcerations about the nails noted in some of his cases by the same 
physician. 



SOMNIFACIENTS 83 

In die third group of oases, petechia, ecohymoses, ulcerations, and even high 
fever and other pyemic symptoms, arc asserted to have been produced by the con- 
tinuous use of chloral. It seems to us, however, very doubtful whether the drug 
really was the cause of I he symptoms which have been recorded by Crichton Brown, 
by Monkton, and by Kirn. 

The habitual use of chloral as a narcotic has been indulged in, it is 
asserted, to a considerable extent, and George F. Elliott reports symp- 
toms like those of delirium tremens as following the withdrawal of the 
accustomed draughts. 

SULPHONES. 

The group of hypnotics known as the sulphones which were 
discovered by E. Baumann in 1866, include a number of compounds 
in which the hydrogen atoms of methane are replaced by alkyl- 
sulplionic radicals. The two most employed in this country are 
the so-called sulphonal (diethylsulfonedimethylmethane), and trional, 
(diethylsulphonemethylethylmethane). The original statement of 
Baumann and Kast that the hypnotic powers of these drugs is in 
direct relation to the number of ethyl radicals in their chemical 
make up has been confirmed by Diehl. 

Sulphonal and trional are both of them colorless crystalline pow- 
ders; the former is practically tasteless but trional has a slightly 
bitter flavor. Sulphonal is practically insoluble in cold water, but 
sparingly soluble in alcohol and in ether. Trional is also almost 
insoluble in water — requiring nearly 200 times its weight of water to 
dissolve it — but is readily soluble in both alcohol and ether. 

Official Preparations : 

Sulphonmethanum [Sulphonal] 30 to 45 grains (2-3 Gm.). 

Sulphonethylmethanum [Trional] 10 to 30 grains (0.6-2 Gm.). 

Absorption and Elimination. — Both of these drugs, owing to their 
slight solubility, are absorbed with great slowness, but of the two 
sulphonal is distinctly the slower in its action, requiring sometimes 
two hours for the manifestation of its effect. The elimination like- 
wise takes place very slowly so that, after the use of sulphonal, 
drowsiness is frequently manifested the next day. When taken in 
large amount they escape to some extent through the kidney un- 
changed, but the greater portion is converted into an organic sulphur 
compound, which, according to the researches of W. J. Smith (con- 
firmed by Baumann and Salkowski), is probably ethyl- sulphonic acid. 

Physiological Action. — The sulphones as far as we know have 
very little effect upon the general system, the action being limited 
almost solely to depression of the brain. There is some evidence of a 
slight stimulant influence upon the spinal cord. The effects upon the 
circulation are practically nil. 

In the frog, the dog, and the rabbit the sulphones produce sleep, which, if the 
dose be sufficiently large, deepens into coma, and is accompanied by paresis, tremors, 
and convulsions. Knoblauch affirms that not infrequently the loss of power in the 



84 GENERAL REMEDIES 

hind legs precedes sleep, and that weakness and ataxia are prominent symptoms 
after large doses. The convulsions, which are said to be epileptic, are produced by 
very large toxic doses only. 

According to Haenel, the rate of the mental function is distinctly lessened by 
trional and continues slow for some time after the sleep period. If it be true, as 
asserted by Egasse, that in animals trional sleep is attended by increase in the 
activity of the reflexes, it probably stimulates the spinal cord. According to Shick 
sulphonal usually lessens spinal activity, by stimulation of Setschenow's centre, 
although in some of his experiments the reflexes were increased. The same author 
reports that it has no influence upon the motor or sensory nerves, nor upon the 
muscles . 

Kast found tliat there is neither microscopic nor spectroscopic blood changes 
in animals acutely poisoned by sulphonal. 

According to Kast, the blood-pressure is not altered by doses which produce 
sleep, and the rise of arterial pressure noticed by Shick in non-curarized animals 
may have been produced by failure of respiration. 

Kronfeld, as the result of sphygmomanometrical studies, affirms that the 
blood -pressure is always lowered during sleep caused by trional, the fall being due, 
in his belief, to depression of the vaso-motor centres. 

Therapeutics. — The sulphones are valuable hypnotics in ner- 
vous insomnias but have little or no analgesic effects. Of the two 
here described trional is ordinarily the preferable, being more prompt 
and certain in its effect as well as less liable to cause toxic manifesta- 
tions from prolonged use. Sleep usually develops in from a half to 
one hour after the dose, in most cases gradually, but sometimes with 
abruptness. It is usually quiet, and not followed by any disagreeable 
after-effects, although sometimes mental confusion and lassitude 
remain during the following day; these after-results being, in our 
experience, especially likely to occur in cases in which there is a distinct 
depression of the brain-nutrition. Where the sleeplessness is due to 
pain, the sulphones are usually not serviceable; but in the insomnia 
of insanity it often acts well. Later experience, however, does not 
seem to carry out the original assertion of Kast, that sulphonal is 
especially useful in cases of insomnia from cardiac diseases. In such 
affections it appears to be not only an uncertain, but even a dangerous 
drug, inferior to chloral.* At present this disagreeable action of the 
drug does not seem to be explainable by any influence exerted upon 
the heart. It is possible that it is due to irritation of already congested 
kidneys. 

Sulphonal has been used with asserted good results in epilepsy, 
hiccough, chorea, and nocturnal cramps; according to E. Andrews, 
it is very effective against the spasm of fractures. It has also been 
commended as a sexual sedative in chordee and spermatorrhoea. In 
our own practice, sulphonal given an hour after meals has seemed 
to have value as an intestinal antiseptic. It is asserted that it is a 
very useful remedy in colliquative night-sweats. 

Administration. — The sulphones are absorbed with difficulty, 
and should always be administered in fine powder diffused in water 
or milk, or enclosed in capsules. We have seen compressed pills of 

* See Joachiam (Therap. Moiiatsh., iii.); also Schmey (Ibid., 1888, ii.), 



SOMNIFACIENTS 85 

sulphonal pass through the body unchanged, and have no doubt that 
the reported great slowness or even failure of act ion has often depended 
on improper methods of administration. It should be an invariable 
rule, when sulphonal is given continuously, to interrupt its use for 
at least four days every two weeks so as to allow the system to clear 
itself; and the urine should be watched and the first sign of a pinkish 
hue be the immediate order for the withdrawal of the drug. Also 
attention should be paid to having a daily free evacuation of the 
bowels. 

Toxicology. — Although occasionally even the single dose of 
sulphonal produces nausea (even severe gastric pain: Dauthville), 
languor, headache, depression, or pronounced mental disturbance, 
poisoning from a single dose of either of these drugs is very rare, 
probably on account of the slowness of absorption. The statement 
sometimes made, however, that the single dose is incapable of taking 
life is untrue at least for sulphonal. 

Petitt states he has seen coma ending in death produced in a woman by two 
grammes of sulphonal. In a case recorded by G. Hoppe-Seyler and Ritter fifty 
grammes produced death in seventy hours, the symptoms having been coma, cyano- 
sis, and high fever. The expired air had the odor of mercaptan, and the urine 
contained unaltered sulphonal. Pronounced fatty necrosis of the intestinal and 
renal epithelium, fatty degeneration of the heart, and broncho-pneumonia were 
found in the body. The broncho-pneumonia was believed by Hoppe-Seyler to be 
the result of the aspiration of the contents of the mouth and gullet, due to the 
insensibility of the epiglottis. 

In one case recovery occurred after one hundred and twenty grains of sulphonal, 
although there were complete abolition of the reflexes and loss of the radial pulse.* 
E. Neisser has recorded a case in which one hundred grammes caused a profound 
sleep lasting ninety hours, a fall of bodily temperature to 96° F., and a symmetrical 
minutely papulous eruption upon the hands, but no great disturbance of the heart 
or breathing or of the reflexes; after recovery there was a marked ataxia of speech 
and movement which disappeared in a week. 

Sixty grains of trional have produced hematoporphyrinuria (Berger), but 120 
grains have been recovered from with almost no symptoms (Collatz). Wightwick 
and Rolleston report a case in which 120 grains caused dilated pupils, loss of reflexes 
and cardiac depression 

On the other hand serious and even fatal chronic poisoning from 
the prolonged use of these remedies is unfortunately not rare. The 
condition is more common from sulphonal, but trional has in several 
instances given rise to similar symptoms. The mortality in chronic 
sulphonal-poisoning has been extremely high. 

Although prodromic symptoms probably always usher in chronic 
sulphonal-poisoning, they are so slight and so lacking in anything 
characteristic that in a large majority of cases the condition appears 
to develop abruptly, and usually, notwithstanding the suspension of 
the remedy, continues to the fatal issue, death occurring in about 
seventy-five per cent, of the cases. The first manifestations are 
increasing lassitude and weakness, nausea, and gastro-intestinal 

* See B. M . </., 1899, ii. 8. 



86 GENERAL REMEDIES 

disturbance as shown by diarrhoea or constipation. Ordinarily the 
first symptom noted is the pink coloration of the urine, which deepens 
until the fluid becomes of a dark red color, staining the linen upon 
which it falls. Usually this coloration of the urine is soon followed 
by obstinate constipation, violent vomiting, spasm of the abdominal 
muscles, and tenderness upon pressure in the region of the liver and 
stomach. At the same time there develop insomnia, ataxia, sup- 
pression of perspiration, paresis of the upper extremities or of irregular 
groups of muscles, pronounced weakness of the legs, loss of the patellar 
and other reflexes, paresthesia, various forms of skin eruptions, mus- 
cular spasms, and finally a condition of profound collapse, with 
highly acid, albuminous, hemorrhagic, or suppressed urine, ending 
in death. After death, widespread fatty degeneration, involving 
in some cases the heart, but especially affecting the liver and kid- 
ney, has been found. Erbsloh has reported multiple peripheral 
neuritis from the prolonged use of sulphonal. 

In some cases the renal changes have been confined to a glomerular 
or»cortical nephritis,* with or without hemorrhage; in other instances 
the destruction of the kidney has been more complete. The most 
characteristic symptom is the appearance of hematoporphyrin in 
the urine; its recognition is best made with the spectroscope. 

The symptoms caused by trional are practically the same as those 
just described although the premonitory manifestations are usually 
more marked. Hart has reported double wrist-drop, probably due 
to peripheral neuritis. 

It has been shown by Salkowski (confirmed by Kast) that ethyl-sulphonic 
acid is not poisonous, and hematoporphyrin appears also to be free from toxic 
properties; so that the symptoms of chronic poisoning are probably due to an 
accumulation of the sulphone in the system, and are of largely primary and not of 
secondary character, though some of them may be in fact uremic. The explanation 
of the occurrence of hematoporphyrinuria is at present very difficult; f frequently 
it does not come on until several days after the ingestion of the last dose. In a fatal 
case of acute poisoning reported by Hoppe-Seyler and Ritter it was not present. 
As has been demonstrated by Garrod and Hopkins, the urine of patients taking 
sulphonal does not ordinarily contain more hematoporphyrin than is often seen in 
health. It is generally thought the hematoporphyrin is a decomposition product 
of hematin, and Stokvis believes that the hematoporphyrinuria is due to the absorp- 
tion of altered blood from hemorrhages which have been produced in the mucous 
membrane of the stomach and intestines by sulphonal, — an explanation which is 
rejected by Kast and Weiss, and also by Garrod and Hopkins, for apparently suffi- 
cient reasons. The observations of Garrod and Hopkins, that the increase of urinary 
hematoporphyrin is not accompanied by a corresponding increase in the excretion 
of iron, and the fact that in the cases recorded by Percy Smith there was no lessen- 
ing in the number of the red blood-corpuscles nor of the hemoglobin, lend prob- 
ability to the assertion of Quincke (confirmed by Herting), that the coloring-matter 
of the urine is not in reality hematoporphyrin, differing from it in its spectroscopic 

* A. E. Taylor and Joseph Sailer (.Contributions William Pepper Lab., Philadelphia, 1900, cxx.) 
found that the degenerated cells of the liver, spleen, lymphatics, and kidney were loaded with 
green pigment, while the blood-serum contained hematoporphyrin. 

t In an elaborate research upon rabbits, Neubauer (.4. E. P. P., 1900, Bd. xliii.) attempted 
unsuccessfully to determine how the hematoporphyrin is produced by sulphonal. In agreement 
with Kast and Weiss, he was unable to produce hematoporphyrin by digesting the normal organs 
of the rabbit with sulphonal. 



SOMNIFACIENTS 87 

lines. Franz Midler, however, found in a caso of sulphonal-poisoning which recov- 
ered that the hemoglobin fell during the period of red urine to forty-five per cent., 
returning afterwards to eighty-five per cent. ; while Hoppc-Seyler believes that 
the anatomical changes in sulphonal-poisoning are really secondary to the 
destruction of the red blood-disks. 

In tho treatment of chronic sulphone-poisoning the most important 
measure is to see that the bowels are thoroughly opened and cleaned 
of any undissolved drug which may be lying there and by slow absorp- 
tion making the patient's condition continually more hopeless. For 
this purpose heroic measures are often necessary and vital time should 
not be lost experimenting with the milder cathartics. After this the 
poison should be diluted and elimination encouraged by the free use 
of water. This may best be given by hypodermoclysis of physiological 
salt solution as well as by the ingestion of water by mouth. The 
use of the alkaline carbonates, as suggested by Miiller, is probably 
also of service.* For the heart-failure and other symptoms the appro- 
priate drugs should be administered, but they usually have very little 
effect. 

PARALDEHYDE. 

This substance, which is a polymer of acetaldehyde, occurs as 
a colorless liquid, with a strong and disagreeable odor and a burning 
taste. It is soluble in 8 parts of cool water, less soluble in warm water, 
and mixes in any proportions with alcohol or ether. 

Paraldehydum \ to 1 fluidrachm (2-4 C.c). 

Local Action. — Paraldehyde is locally irritant, and is likely, when 
taken in large doses, to disturb the stomach, or at least to give rise 
to disagreeable eructations. 

Absorption and Elimination. — Absorption of paraldehyde com- 
mences at once, and its action is usually manifested in a few minutes. 
Its elimination begins promptly, but is carried on slowly, so that the 
breath frequently reeks of it for hours after the patient has awakened. 
Its chief channel of escape is probably through the respiratory organs, 
but it has been found in the urine by Gordon and Raimann, and 
Raimann also believes that it escapes to some extent with the 
perspiration. It appears not to be destroyed in the system. 

Physiological Action. — According to the physiological studies of 
Cervello, Prevost, and Gordon, the injection of from one-half to one 
drachm of paraldehyde produces in the rabbit and dog loss of sensi- 
bility, and in a very short time deep sleep with general muscular 
relaxation, some slowing of the breathing and of the rapidity of the 
heart, without, however, distinct lowering of the blood-pressure. 
After very large doses reflex excitability is abolished, and death takes 
place through respiratory paralysis, the cardiac action and blood- 
pressure long resisting the action of the drug. In man paraldehyde 

* Alkaline waters, however, in Pollitz's case (Vierteljahr. /. Gerichtl. Med., 1898, v.) apparently 
failed to do any good. 



88 GENERAL REMEDIES 

produces a deep sleep, with, if the dose have been large enough, loss 
of reflex activity, some slowing of the respiration and pulse-rate, 
and slight fall in the temperature. The symptoms usually pass off 
without disagreeable after-effects, but after very large doses there 
are sometimes malaise, headache, giddiness, nausea, or even vomiting. 
Usually there is some diuretic action. 

Nervous System. — Paraldehyde* probably produces sleep by a 
direct action upon the cerebral cells. Bokai and Barcsi have found 
that there is marked relaxation of the cerebral bloQd-vessels, but this 
is probably the result, not the cause, of the arrest of brain function. 
The characteristic effect of the drug upon muscular action is depres- 
sion, which is probably of spinal origin, though this has not been 
absolutely proved. Bokai and Barcsi affirm that after small doses 
there is a period of heightened reflexes. 

Circulation. — Upon the circulation paraldehyde has very little 
influence, nor is the blood itself affected except by the very largest 
doses. According to Henoque, intravenous injections of paraldehyde 
in the animal are followed by disappearance of the absorption-band 
in the yellow-green of the oxyhemoglobin spectrum. 

Nutrition. — According to Dockendorff, the elimination of nitrogen 
and phosphorus is somewhat lessened by paraldehyde, and in cases 
of chronic poisoning in man the elimination of phosphates has been 
found to be very low. Hemoglobinuria has been noticed in the horse, 
but not in other animals poisoned with paraldehyde. 

Therapeutics. — Paraldehyde is a very useful hypnotic in the 
numerous cases of mild insomnia, such as is seen in neurasthenia, and 
is also used as an adjuvant to other remedies in delirium tremens, 
insanity, and the more serious forms of morbid wakefulness not depend- 
ent upon pain. It is one of the most prompt, as well as safe, of the 
somnifacients. 

Toxicology. — Very large doses of paraldehyde have been taken 
without fatal results, although death is alleged to have been pro- 
duced by four ounces (Drage). In one case reported by Raimann, 
nearly eight hundred grains produced simply deep sleep lasting 
nineteen hours, without evil result. Probst reports one case in which 
nine hundred grains gave sleep lasting tAventy-two hours, without 
serious symptoms; and another in which nearly five ounces of paralde- 
hyde, taken within thirty-six hours, produced profound coma, marked 
lividity, excessive muscular relaxation and vomiting, slight fall of 
temperature, without pronounced depression either of the heart's 
action or of the blood-pressure, and without complete loss of the 
reflexes. The urine at first was in no way abnormal; later it contained 
acetone. On the second day mental aberration appeared and con- 
tinued, and on the fifth day distinct tremors appeared: by the seventh 
day the case was convalescent. Although chronic poisoning has 
frequently been produced by paraldehyde, we know of no recorded 

* Cappelli and Brugia have also noted lessening in the size of the brain under the influence 
of paraldehyde, in a man suffering from defect of the skull. 



SOMNIFACIENTS 89 

fatal case. Disturbances of the digestion are common. More charac- 
teristic is a psychic disturbance somewhat resembling delirium 
tremens and in many cases associated with tremors and muscular 
weakness. These symptoms usually subside with the cessation of the 
taking of the drug. In one case thirty-five grammes were taken 
daily for a year. In a second case five grammes were taken daily for 
thirteen years, without the production of any symptoms.* In the 
experiments of Bokai and Barcsi it was found possible to produce in 
the animal, by the" continued use of paraldehyde, fatty degeneration 
of the liver and of the heart-muscle, but no such result has been noted 
in man. In some cases nasal ulcers, skin eruptions, and various 
vaso-motor disturbances are said to have been produced by the long 
administration of the drug. 

Ethyl Carbamate. — The ethyl ester of carbamic acid, commonly 
called urethane, occurs in the form of odorless columnar crystals or 
scales, of a cooling, saline taste, soluble in less than one part of water. 
It was originally proposed by Schmiedeberg as an hypnotic which 
acts directly upon the cerebral cortex, depresses the motor side of 
the spinal cord, but has very little influence upon the circulation, the 
arterial pressure remaining normal even during deep narcosis. Clinical 
experience has shown that urethane is safe but somewhat uncertain 
in its action, and that it may be used, sometimes with satisfactory 
results, as an hypnotic and also as an anti-convulsant in puerperal 
and other serious eclampsia as well as in tetanus. 

iEthylis Carbamas [Urethane] 15 to 30 grains (1-2 Gm.). 

Chloralformamide. — Under the name of chloralformamide, a 
compound of anhydrous chloral and formamide has been used as an 
hypnotic and has been made official in the U. S. Pharmacopoeia. 
It is a slightly bitter crystalline substance, soluble in 18.7 parts of 
water and 1.3 parts of strong alcohol. It is decomposed by hot water, 
but its solution in cold water is moderately permanent; it is rapidly 
decomposed by alkalies. In the lower animals chloralformamide 
produces lethargy, narcosis, sleep, and, finally, if it has been taken 
in sufficient amount, death from failure of respiration. According 
to Langgaard in the rabbit the sleep is accompanied by pronounced 
decrease in the amount of air drawn in and out of the lungs and pro- 
nounced lessening of the blood-pressure. These results, however, 
are scarcely in accordance with those of other observers. Otto Halasz 
found the blood-pressure very slightly affected. Von Mering and 
Zuntz have shown that the fall in the air movements of respiration 
obtained by Langgaard was not greater than that which results from 
sleep, and also obtained deep sleep and even complete anesthesia in 
the rabbit without fall of the arterial pressure. 



V. A. S., 1887, xiv., and Cb. N., 1900, p. 139. 



90 GENERAL REMEDIES 

In a series of experiments made by David Cerna and H. C. Wood 
in the laboratory of the University, it was found that the influence of 
chloralformamide upon the circulation is very feeble, only the largest 
toxic dose lowering the arterial pressure at all. In the dog the respira- 
tions were always enormously hurried by the drug, although no 
experiments were made to determine the absolute amount of air 
moved. The action of the drug upon the spinal cord was also very 
feeble, and no perceptible influence was shown upon the nerves and 
muscles; but the effect upon the cerebral cortex was very pronounced. 

Chloralformamidum [Chloralamid] 20 to 40 grains (1.3-2.7 Gm.). 

Therapeutics. — Chloralformamide is a rather slowly acting and 
uncertain hypnotic, which usually does not cause any unpleasant 
after-effects, but sometimes produces confusion, giddiness, and 
headache. It has been especially recommended by Hagemann and 
Hurler for the relief of cardiac asthma. Our knowledge of its physio- 
logical action seems to show that the assertions of various clinicians, 
that it is better borne than hydrated chloral in cases where there is 
cardiac weakness, have a foundation in fact. It should be given 
in watery solutions or capsules half an hour before the expected time 
of sleep. 

Amylene Chloral. Dormiol. — This drug, formed by the union of chloral 
and amylene hydrate, is a colorless, oily liquid with a camphor-like odor, insoluble 
in water. There is much recorded clinical evidence as to its value in insomnia 
which is not dependent upon the existence of pain. It has been largely employed 
in insane asylums, and it is asserted that it has no disagreeable after-effects; that 
it is not depressant to the heart, and may be used in cardiac insomnia; and that 
when continuously exhibited it does not produce chronic poisoning. Its action is 
prompt, but somewhat fugacious, and patients rapidly become accustomed to its use. 
Dose, from ten grains to one drachm (0.6-4 Gm.) in capsules or dropped in cold water. 

Hedonal (Methyl-propyl-carbirwl-urethane). — This occurs in colorless cystals, 
sparingly soluble in cold water, of a disagreeable somewhat menthol-like taste, 
which are believed to split up in the system into carbon dioxide, ammonia, and 
urea. It has been brought forward as an hypnotic, which in severe cases of insom- 
nia or when the patient is kept awake by pain, is of little service, but is valuable in 
mild cases on account of having no disagreeable after-effects. No cases of poisoning 
by it have been reported, and so far its prolonged use has not been followed by 
disagreeable symptoms. It is not known to have any influence upon the circulation, 
and, resembling trional in its action, has been especially commended as an alterna- 
tive to that drug. Probably owing to the formation of urea, it sometimes acts as a 
diuretic, and, according to De Moor, this action is much increased by its adminis- 
tration in solution. Dose, from fifteen to forty-five grains (1-3 Gm.), preferably 
administered in capsules half an hour before the desired effect. 

Isopral (Trichlorisopropylalkohol). — This substance, readily soluble in water, 
alcohol, or ether, has a camphor-like odor and aromatic taste. According to Im- 
pens, it is readily absorbed through the skin, the subcutaneous tissue, and the 
digestive tract, its effects when taken internally being manifested in from three 
to five minutes. The claim of Impens that it is only half as toxic in proportion to 
its somnifacient power as hydrated chloral has been contradicted by Hatcher, 
who finds that while it is somewhat more powerful it is also more toxic than hydrated 
chloral and is a powerful depressant to both the circulation and respiration. 



SOMNIFACIENTS 91 

VahoNAi (Di-cilii/l-nuilitiu/l-uira). — This drug occurs in odorless, colorless, 
slightly bitter crystals, soluble in one hundred and forty-five parts of water at (>s° F. 

Originally brought forward by E. Fischer and J. von Mering as an hypnotic, 
veronal has been tested by various clinicians in all forms of insomnia, with reports 
which arc very favorable. It Has been found by Mendel and Kron and by Weber* 
to Ik- especially valuable in the treatment of insomnia- with motor excitement or 
active hallucinations, also in depressive insanity; contrary to the statements of 
some clinicians, Mendel and Kron deny its value as an antineuralgie. Concerning 
its general physiological action we have little knowledge, but C. Trautmann affirms 
as the result of experimental studies that it lessens nitrogenous elimination. Vari- 
ous authorities asseii thai ii leaves no after-effects; but Jolly, Rosenfeld, and 
WOrth have noticed alter its taking, malaise, headache and giddiness, and even 
disturbances of speech, chiefly when it has been given in very large doses. Fatal 
cases of poisoning by veronal have been reported by Germann (200 grains) and 
Barncomb. 

Originally recommended in doses of half a gramme, veronal has been given 
practically up to one and a half grammes, but has been reported by various observ- 
ers as efficient in much less amount; so that at present from ten to fifteen grains 
(0.6-1 Gm.) may be considered as its dose.f 

Chloralose occurs in small crystals, having a very bitter and disagreeable 
but not acrid taste. It is freely soluble in hot water, slightly so in cold water. It 
was first brought forward as a remedial agent by Hanriot and Richet, who state 
that five grammes of it will produce in a dog of ten kilogrammes' weight symptoms 
of intoxication followed by a most profound sleep in which all sensibility is lost, 
although the reflex activities are greater than normal; that upon the circulation 
it has but little power, the arterial pressure, even when there is profound uncon- 
sciousness, being scarcely affected; that during the unconsciousness not only is 
the motor side of the spinal cord more active than normal, but the cerebral cortex 
is excessively excitable, the animals experimented upon offering a strong contrast 
with chloralized dogs, in which the cerebral cortex is almost devoid of responding 
power. The statements of its discoverers, that, taken in doses of five grains, it would 
produce in man a profound sleep lasting for many hours, and not followed by un- 
pleasant after-effects, have not been sustained. Its action is very variable; the 
dose of ten grains will in many cases produce no effect, and yet in other cases has 
caused complete unconsciousness with marked cyanosis and slowing of the pulse. 
Its therapeutic influence has frequently been attended by very unpleasant symp- 
toms, such as tremors, partial or general paralysis, great slowing of the pulse and 
cardiac depression, involuntary discharge of urine during sleep, excessive vomiting, 
and delirious intoxication. In our experience, although occasionally useful, the 
drug has not proved generally satisfactory. Dose, from five to ten grains (0.3-0.6 
Gm.)4 

Chloretone, Acetone-chloroform, or Trichlor Tertiary Butyl Alcohol, is a white 
crystalline compound with a eamphoraceous odor; very soluble in strong alcohol 
and ether, soluble to the extent of about one per cent, in cold, more soluble in 
boiling, water. § 

Physiological Action. — In proper dose chloretone causes in the lower 
animals a profound sleep, with complete and prolonged anesthesia, without marked 
effect upon the respiration or blood-pressure. This condition may be continued 
as long as four days, and the animal wake unharmed; but if the dose has been 

* For references, see D. W. M., 1903, pp. G08, 726. 

t Hee S. Jb., Bd. eclxxviii., celxxix, for abstracts of the literature to date; also Ther. Gaz., 1903. 

t See Brit. Med. Journ., 1893, ii. For cases of unpleasant action, see Schmidt's Jahrb., ccxlv.; 
also Revue Neurolog., 1894, ii. 

§ Chloretone was discovered by Willgerodt in 1881, and suggested as a substitute for chloral 
by him in 1884. In 1891 John J. Abel began to experiment with it, and in 1894 demonstrated its 
usefulness as a practical hypnotic and anesthetic for the physiologist (see Science, January, 1895). 

Abel states that Faust has found that urethane and chloretone rubbed together make a fluid. 
The physiological properties of this substance do not seem to have been investigated. 



92 



GENERAL REMEDIES 



sufficient, after several days of sleep death occurs from asphyxia. According to 
E. M. Houghton and T. B. Aldrich, applied locally to the frog's heart, it slows the 
rate and produces a more complete systole, and lias no action upon the blood itself. 
Locally applied it is a sensory nerve paralyzant. Houghton and Aldrich having 
foiled to detect it, acetone, or chloroform in any of the excretions of the poisoned 
animal, believe that it undergoes decomposition in the body. 

Therapeutics. — Chloretone lias proven to be a very uncertain hypnotic* 
and to-day is comparatively little employed except as a local remedy. It appears 
to possess both antiseptic and anesthetic powers and is applied to foul, irritable 
ulcers and wounds. It lias also been employed in doses of from five to eight grains 
in vomiting, gastric cancer, and other painful local conditions of the stomach. As 
an hypnotic it has been used in ordinary insomnia, delirium tremens, and various 
forms of insanity, but is uncertain in its action. According to Wharton Sinkler, 
it is useful in epilepsy, and especially in petit mal, in doses of from three to five 
grains (0.2-0.3 Gin.), three times a day. 

We know of no deaths reported from chloretone; one hundred and twenty 
grains taken during twenty-four hours (W. M. Donald) caused profound sleep 
lasting for six days, without any untoward symptoms except gastric irritability. 
The pulse ranged from 85 to 104, and the bodily temperature fell to 96° F. 

The dose of chloretone has been set down from twelve to fifteen grains (0.8-1 
Gm.), but we have exhibited thirty grains in the twelve hours without the produc- 
tion of any symptoms whatever; and Wade, who has used the drug largely, gave 
the average dose as from thirty-five to fifty grains- 



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hypnotic than chloral, the ratio of the somnifacient to the fatal dose being only as 1: 1.7. 



SOMNIFACIENTS 



93 



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DaUTHVILLE Thesis, I'aris, 1889. 

EoASSE B. G. T., 1894, ii. 

Erbsloh D. Z. N., 1903. 

Garrod and Hopkins. J. P. and B., 1895-96, 

iii. 
IIm.nki Psvcholog. Arbeit., 1897, ii. 

Hart A. J. M. S., 1901, exxi. 

Hertinq S. Jb., 1894, ccxliv. 

Hoppe-Skyi.kr and Ritter.S. .11)., cexxvii.194. 

Kast B. K. W., 1888. 

Kast A. E. P. P., 1892, xxxi. 

Kast and Weiss. B. K. W., 1896, xxxiii. 

Kronfeld W. M. Bl., 1898, xxi. 

MiiLLER W. K. W., 1894, 252. 

Neisser S. Jb., cexxxi. 

Petitt M. News, 1899, lv. 

Smith Pract., 1889 and 1892. 

Stokvis S. Jb., ccxlviii. 

Wightwick and Rolleston L. L., 1903, i. 
1096. 

PARALDEHYDE. 

Bokai and Barcsi.P. M. C. P., 1885-86. 
Cappelli and Brugia..A. I. M. N., 1886, i. 

Drage L. L., Sept. 1900. 

Probst M. P. N., 1903, Bd. xiv. 

Raimann W. K. R., 1899, Nos. 19, 20, 

21, 22. 

MINOR HYPNOTICS. 

Donald T. G., Jan. 1900. 

Farncomb Canad. Pract. and Rev., xxx. 

681. 
Fischer and von Mering. .Ther. Geg., v. 97. 

German J. A. M. A., xlvi. 1899. 

Hatcher J. A. M. A., xlviii. 184. 

Hai.asz W. M. W., 1889. 

Hagemann and Hufler. .M. M. W., 1889. 
Hanriot and Richet. .C. R. S. B., 1893. 
Hodghton and Aldrich. . J. A. M. A., Sept. 

23 1899. 

Impens Th. M., Sept. 1903. 

Langgaard Th. M., 1889. 

Schmiedeberg . . . A. E. P. P., xx. 210. 

Sinkler T. M., July, 1901. 

Trautmann Ther. Geg., 1903. 

Wade J. N. M. D., 1900. 



FAMILY IV.— DELIRIFACIENTS. 



In the present group are considered medicines whose preparations, 
when taken into the system, cause marked dilatation of the pupil 
and act upon the cerebral nerve-cells so as to produce delirium. 

Most of these belong to the Solanacese, or nightshade family. 
This is one of the most remarkable groups of plants in all the vegetable 
kingdom; it yields such common vegetables as the potato and tomato, 
as well as tobacco and a number of other powerful poisons. The 
most important plants, from a therapeutic standpoint, belonging to 
this family are the Atropa belladonna, the Datura stramonium, the 
Scopola carniolica and the Hyoscyamus niger. From these and allied 
plants a large number of alkaloids have been isolated. Many of these 
which have been thought to be pure principles have been shown 
subsequently to be simply mixtures of previously discovered bases. 
The most important alkaloids found in these plants are atropine, 
hyoscyamine* and hyoscine. 

Atropa belladonna (deadly nightshade) is an herbaceous perennial, 
native to Europe. The leaves and root are both official. The leaves 
(Belladonnae Folia) are four to five inches long and two to four inches 
broad, ovate, with entire margin. The root (Belladonnae Radix) 
occurs in brown wrinkled pieces about the thickness and length of 
the finger, somewhat tapering. Belladonna leaves should contain 
not less than 0.3 per cent, of mydriatic alkaloids, of which the most 
important are atropine and hyoscyamine. The root should contain 
0.45 per cent, of the same alkaloids. 

Stramonium is the leaves of Datura stramonium, or jimson-weed, 
a common plant growing in waste places in many parts of the United 
States. The plant is characterized by the vivid green color of its 
leaves, white to purplish flowers and a peculiar thorny fruit which 
gives to it the name of "thorn apple." The leaves are from four to 
five inches long and deeply toothed. The alkaloid daturine, which has 
been described as its active principle, seems to be a mixture of atropine 
and hyoscyamine, and is present in the proportion of 0.25 per cent. 

* Atropine and hyoscyamine are isomeric compounds. They may be easily distinguished 
however by their relations to polarized light. Whereas hyoscyamine rotates polarized light to 
the left, atropine is without rotatory power. According to Amenomiya (Archiv der Pharmacie, 
1902, 240, p. 498) atropine is, however, a mixture of a lsevo- and a dextro-rotatory substance result- 
ing in an optically inert body. Cushny {J. P., 1903, vol. 30, p. 177) found that hyoscyamine 
qualitatively acted like atropine but that it was twice as powerful in its effects upon certain nerve 
terminals, as the vagi, glands and the pupil, and was less active as a convulsant. He reasoned that 
the la?vo-hyoscyamine affected chiefly the peripheral nerves and that the dextro-hyoscyamine 
affected more powerfully the central nervous system. A few experiments made with the dextro- 
hyoscyamine by Amenomiya seemed to confirm this deduction, this substance being only one- 
tenth as active in its effects upon the peripheral nerves as the larvo-hyoscyamine. There appear 
similarly two varieties of hyoscine (see p. 108). For all practical purposes hyoscyamine and atro- 
pine mav probably be properly considered as identical in their effects. (See Shaw, Richter, Ringer 
and H. C. Wood, Jr.) 

94 



DKLIR1FACIENTS <). r , 

H yoscyamus niger, or henbane, is a European plant, of which the 
leaves are official. These somewhat resemble the leaves of the stra- 
monium but are larger. They contain 0.08 per cent, of alkaloids, 
mostly hyoscyamine, with some hyoscine; the latter alkaloid is 
generally believed to somewhat modify the dominant action of 
hyoscyamine. 

Scopola is a rhizome of Scopola carniolica, a European plant, 
very similar to, if not identical with Scopola japonica, or Japanese 
belladonna. It contains 0.5 per cent, of total alkaloids, chiefly 
hyoscyamine, with some hyoscine and atropine. 

Official Preparations : 

Extractum Belladonna* Foliorum J to J grain (0.008-0.031 Gin.). 

Tinctura Belladonnas Foliorum (10 per 

cent.) 10 to 30 minims (0.6-2.0 C.c). 

Fluidextractum Belladonna Radicis 1 to 2 minims (0.06-0.12 Co.). 

Linimentum Belladonna? (5 per cent, cam- 
phor in fluidextract) External use. 

Emplastrum Belladonna? External use. 

Extractum Stramonii i to J grain (0.008-0.031 Gm.). 

Fluidextractum Stramonii 1 to 2 minims (0.06-0.12 C.c). 

Tinctura Stramonii (10 per cent.) 10 to 30 minims (0.6-2.0 C.c). 

Unguentum Stramonii External use. 

Extractum Hyoscyami 1 to 3 grains (0.06-0.19 Gm.). 

Fluidextractum Hyoscyami 3 to 5 minims (0.2-0.3 C.c). 

Tinctura Hyoscyami (10 per cent.) \ to 2 fluidrachms (2-8 C.c). 

Extractum Scopola? \ to \ grain (0.008-0.016 Gm.). 

Fluidextractum Scopola? 1 to 2 minims (0.06-0.12 C.c). 

The following alkaloidal preparations are also recognized: 

Atropina ^ u to ^ grain (0.3-1.0 Milligm.). 

Atropina? Sulphas ^ 7 to ^ grain (0.3-1.0 Milligm.). 

Oleatum Atropina? (2 per cent.) External use. 

Hyoscyamina? Hydrobromidum ^ to -fa grain (0.3-1.0 Milligm.). 

Hyoscyamina? Sulphas r J 7 to ^- - grain (0.3-1.0 Milligm.). 

ATROPINE. 

Atropine occurs in silky prismatic and acicular, often aggregated, 
crystals, of a bitter, burning taste, without odor, practically insoluble 
in water, and therefore always used in the form of the sulphate. It 
is most abundant in the root, and, according to M. Lefort, in that of 
young plants. 

Physiological Action. — Local Action.— Elimination. — Atropine is 
not irritant, but when locally applied in sufficient concentration is 
probably paralyzant to most of the higher forms of protoplasm, over- 
powering the capillary walls, the sensory and motor nerves, and even 
muscular and glandular cell-action. A. Zeller has found that a one- 
per-cent. solution of atropine brought in contact with the blood, 
outside of the body, checks the movements of the corpuscles. 

Atropine is absorbed with great rapidity from the primae via? and 
slowly but certainly through the skin. It is eliminated in great part 



96 GENERAL REMEDIES 

or altogether unchanged, chemists having failed to find in any secretion 
the natural decomposition product, ecgonine, and Wiechowski having 
recovered, on an average, thirty-three per cent, of the injected atro- 
pine from the urine. It has been found in all the tissues of the poisoned 
individual, and S. Fubini and O. Bonanni have detected it in the milk, 
but it chiefly escapes by the kidneys; hence poisoning may often 
be diagnosed by dropping the urine of the patient in the eye of a cat 
or other domestic animal, when mydriasis will be produced. 

Upon the lower animals belladonna to a great extent acts as upon 
man, although its influence is much less powerful in them, and very 
much larger doses are required. 

In their sensitiveness to atropine animals differ very much, and, as a general 
rule, herbivora are less susceptible than carnivora. Thus, the rabbit may be fed 
for days entirely upon belladonna-leaves without injury, and many grains of atro- 
pine are necessary to kill it. Pigeons we have found will often recover after the 
hypodermic injection of two grains of atropine, and, according to Fdre, 1.75 grammes 
taken by the mouth will not kill a hen of 2.9 kilogrammes' weight. A very curious 
fact, which we have repeatedly verified, is that the pupils in pigeons cannot be 
dilated by the use of belladonna. According to Richet, the monkey offers an 
extraordinary resistance to the action of atropine. 

Circulation. — Atropine may cause a primary slowing of the pulse — 
very brief and only occasionally to be demonstrated — but the charac- 
teristic results of its administration are rapid pulse with a great rise 
in the arterial pressure. After large toxic doses the rise of pressure 
may be followed by a fall. 

The increase in the pulse-rate is due to the paralysis of the pe- 
ripheral terminations of the pneumogastric nerve, as is shown by the 
fact that electrical irritation of this nerve fails to slow the heart. 
The rise of pressure depends chiefly upon a stimulation of the vaso- 
motor centres and the increase in the rate of the heart, although 
there is some evidence to lead us to believe that the drug exercises 
a slight stimulant influence upon the cardiac muscle. 

The primary fall of the pulse, in accordance with the experiments of Bezold 
and Bloebaum, is due to stimulation of the inhibitory cardiac centre; these ob- 
servers having found that when atropine is injected into the carotid so as to reach 
the pneumogastric centres before the pneumogastric nerve-endings, there is instan- 
taneously a great fall in the rate of the heart's beat. Of course, in the fully atro- 
pinized animal any effect of the drug upon the inhibitory centres is masked by the 
inability of the paralyzed vagi to carry impulses from the centre, and, in fact, only 
in especial cases is the primary slowing manifested.* 

The rise of pressure is due chiefly to stimulation of the vaso-motor centre as 
shown by the fact first demonstrated by Bezold and Bloebaum, and confirmed by 
H. C. Wood, that after section of the spinal cord the alkaloid is powerless to pro- 
duce a rise of pressure. Further Bezold and Bloebaum have found that when 
a small dose of atropine is injected into the carotid artery, — that is, into the 
vaso-motor centres, there is an instantaneous rise of pressure. f 

* See StilU'8 Therapeutics, i. 725. Mitchell, Keen, and Morehouse found it in about one-third 
of the cases after large hypodermic injections, Da Costa in a large proportion {Amer. Journ. Med. 
Sci., July, 1865), and Miss Mary Putnam in some cases {New York Medical Record, 1873). 

t The evidence as to the effect of atropine upon the blood-vessels obtained by direct observa- 
tion of the capillaries of a frog under the microscope on the whole favors the view of vascular 
contraction; but we believe the method of experimentation so fallacious as to be of little evidential 
value. 



DELIRIFACIENTS 



97 



While it may he considered to be established that overwhelming doses of atro- 
pine act as a direct paralyzant to the heart-muscle, the question as to the elTect of 
small doses has been much debated. 

Probably very minute quantities exert a feeble, stimulating influence upon the 
mammalian heart; thus, Kamson discovered that atropine causes in the heart of 
the octopus excitation of the muscular fibre; O. LangendorfT found that when the 
cut-off apex of the frog's heart was touched with a minute quantity of atropine it 




1 


Mlli 


f| 


1 

■ 

■ 











Fig. 



(Normal.) (After atropine.) 

-Effect of Atropine on the Pulse and Respiration. 



Atropine increases the rate of the pulse by paralyzing inhibition ; it stimulates the vaso-motor 
centres, causing a rise of the blood-pressure. It also increases the respiration. Time marker 
indicates 1 second. 

immediately commenced to beat; * and G. Beyer noticed that the ventricles of the 
isolated terrapin's heart are stimulated by minute quantities of the alkaloid, although 
they are arrested in diastole by larger amounts. This action of the drug upon the 
heart -muscle is probably the cause of the increased pulse-rate which has been noted 
as occurring when atropine is given after division of the vagi, although it is possible 
that this increase is due to stimulation of the accelerators.! 



* The reports as to the action upon the rate of the frog's heart are somewhat at variance, 
Bowditch and Luciani having noted an increase, Gnauck a lessening, in the cardiac pulsations 
(Verhandl. Physiolog. Gesellsch. zu Berlin, 1881). H. Schapiro states that this variance is accounted 
for by the fact which he has discovered, that whereas at high temperature (15° C.) the pulsations 
are diminished, at low temperature (7° C.) they are increased. 

t See University Med. Magazine, May, 1891. 

7 



lis GENERAL REMEDIES 

The final fall of blood-pressure in atropine-poisoning is due to its depressing 
influence upon the heart-muscle and upon the muscles in the walls of the capillaries. 
The local application of the alkaloid to the web of the frog's foot is soon followed 
by a complete paralytic dilatation of the vessels; further, Bezold and Bloebaum 
have found that in atropine-poisoning the arterial muscular coats finally lose their 
irritability, but that, so long as they retain it, galvanic stimulation of a sympathetic 
nerve does not fail to induce contraction in the tributary vessels. 

Nervous System.— The delirium which is so characteristic of 
atropine-poisoning shows that it has especial relations with the cere- 
bral cortex. Albertoni finds that neither the single large dose nor the 
repeated continuous dose has any power in preventing the epileptic 
seizure resulting in dogs from the stimulation of the motor zone of 
the cortex: enormous toxic doses seem only to render the response 
slower and less vivid. The influence of atropine upon the psycho- 
motor centres would, therefore, appear to be slight. It should be 
noted that atropine is not in a proper sense hypnotic, the stupor 
which it produces being due to an overwhelming of the cerebral 
cortical centres, and not being preceded by sleep. 

Thomas R. Fraser discovered, in 1869, that if a frog receive an 
injection of about one-thousandth part of its weight of atropine, a 
condition of complete paralysis and obliteration of reflex action comes 
on after a time and lasts from two to four days, to be succeeded by a 
tetanoid stage with violent convulsions of spinal origin and excessive 
excitability of the reflex centres. The explanation of this peculiar 
sequence is not definitely proven. The objection to the theory of 
Fraser that the drug is a spinal stimulant and that the stimulation 
of the spinal cord is masked by a paralysis of the peripheral nerves is 
given below. The most satisfactory explanation as yet put forth 
appears to us to be that which is based upon the theory of the existence 
of a spinal inhibitory centre. 

According to this theory the spinal cord has within it two functions, 
motion and inhibition, certain cells giving off motor impulses, certain 
nerve-fibres inhibiting these motor impulses. In the normal cord the 
motor cells are under continual inhibition; under the influence of 
atropine it is believed that both motor and inhibitory functions are 
paralyzed; hence the general paralysis. After a time, however, the 
motor cells recover themselves so as to be able to generate impulses 
freely, although the inhibitory function of the cord is still depressed, 
the effect being an apparently true spinal excitement, which is due 
to lack of inhibition, the motor cells being actually weak. At such 
a time a peripheral impulse reaching the motor cell, instead of giving 
rise to a simple reflex action, and then being inhibited, passes on and 
starts a series of reflex movements involving all the muscles and 
constituting a tetanic convulsion.* 

* The conjunction of excessive irritability with lack of power in motor cells is a common 
condition in hysteria and neurasthenia. The fact discovered by H. C. Wood, that choreic move- 
ments of the dog are increased by atropine and diminished by quinine, — an inhibitory stimulant, — 
fits very well with the theory of the text, and also with the further facts discovered by E. T. Reichert, 
that if a dog to which a supra-fatal dose of atropine has been given be kept alive by artificial res- 
piration, choreic movements occur which are arrested by intravenous injections of quinine. It 






DELI HI FA( TENTS 99 

In the frog atropine ads as a dopressiint to the peripheral 
endings of the motor nerves although it rarely leads to complete 
paralysis such as is seen after curare. This effect is not demonstra- 
ble in man through the systemic influence of the drug, but may 

be brought out by its local application in the neighborhood of the 
nerve terminals. Atropine appears also to exercise a depressant 
influence upon the sensory nerves although not so marked as on the 

motor trunks. 

It was originally shown by S. Botkin that tying the vessels of a frog's leg so 
as to shut off access of atropine to the nerve, interferes with the paralyzant action 
of the drug in that leg, while in the unprotected leg the poisonous effects of the drug 
were seen; and that the nerves after death from atropine-poisoning have largely 
lost their power of responding to galvanic currents. Fraser confirmed this obser- 
vation — as did also Meuriot and others — and believed that the cause of the primary 
paralysis noted by him was the effect of the drug upon the peripheral nerves. This 
conclusion however has been brought into question by Ringer and Murrell, who 
found that the protection of the nerve-trunks did not hasten a development of the 
tetanus and also that in some instances there was between the stage of paralysis 
and of excitement a stage of normal voluntary and reflex action. 

The action of atropine upon the sensory nerves is similar to its influence upon 
the motor nerves, although less powerful. S. Botkin found that if in the atropinized 
frog the nerve of one leg had been protected from the poison by tying the artery, 
irritation of the foot of the non-protected leg at a time when that leg was com- 
pletely paralyzed would cause spasm in the opposite limb whose motor nerve was 
protected; yet later in the poisoning, although irritation of the foot of the protected 
leg would cause movement in that leg, no irritation of the opposite poisoned foot 
was able to induce response, showing that at first the sensory nerve was intact in 
the paralyzed leg, but that it finally succumbed to the poison. 

Meuriot found that if a frog be bound tightly around the body so as to inter- 
rupt the circulation, and then be poisoned by atropine in the front part of its body, 
at first irritations in any part will give rise to general spasms, but after a time in 
order to get any movements of the hind legs it is necessary to apply an irritant to 
them. Again, the hinder parts of a frog were so bound by ligatures as to cut off 
on the one side all communication except by the nerves, and on the other to leave 
free the nerve and the vessels. A large injection of atropine was then given, and 
followed by strychnine, when it was found that, while irritation of the atropinized 
leg had no effect, stimulation of the non-atropinized leg gave rise to general con- 
vulsions. It is plain, however, that the influence of atropine upon the sensory nerve 
is feeble; for, Botkin found that immersion of a sciatic nerve for some little time 
in a two-and a half-per-cent. solution of the alkaloid did not, in the strychnized 
frog, prevent the nerve transmitting the impulse, since irritation of the foot would 
produce general convulsions. 

Muscles. — The voluntary muscles escape unscathed in atropine- 
poisoning. It is true that Lemattre has shown that the contractility 
of a striated muscle may be destroyed by soaking it in a very con- 
centrated solution of the alkaloid; but long before any such action 
can take place in life the animal is killed; consequently after death 
from belladonna the contractility of the voluntary muscles is found 
unimpaired. 

would appear that choreic movements are the result of inhibitory weakness; that atropine, increas- 
ing inhibitory weakness, increases choreic movements; and that quinine, stimulating inhibition, 
decreases these movements; and that the two alkaloids, so far as inhibition is concerned, are directly 
antagonistic. 



100 GENERAL REMEDIES 

On the non-striated muscles the action of atropine is pronounced, 
but its exact nature is at present writing somewhat uncertain. It may, 
we believe, be considered proved that the toxic dose of atropine 
finally depresses all non-striated muscles; the original assertion of 
Bezold and Bloebaum, that this paralysis may become so complete 
that the strongest faradic currents are unable to cause movements 
either in the intestines, bladder, uterus, or ureters, being probably 
correct. 

The uncertainty is as to the effects of small doses. P. Keuchel 
seems to have proved that by a certain dose of atropine a condition is 
reached in which, although the peristaltic movements of the intestines 
are active, galvanism of the splanchnic — the inhibitory nerves of the 
intestinal coats — fails to have effect. If this be true, atropine para- 
lyzes the peripheral inhibitory intestinal apparatus precisely as it does 
that of the heart. I. Ott states that very minute doses of atropine 
prevent the production of peristalsis by salt placed upon the intes- 
tines, while large doses exaggerate the action of the salt. Admitting 
the correctness of the experiments of Ott and Keuchel, it is evident 
that atropine first stimulates the intestinal inhibitory nervous system 
and then paralyzes it. This, moreover, is corroborated by the fact 
that the smallest dose used by Keuchel was 0.075 grain, by Ott 0.015 
grain, both observers experimenting on the rabbit. When Ott used 
0.45 grain he got the same result as did Keuchel. 

Respiration. — The medicinal dose of atropine ordinarily has no 
apparent effect upon the respiration; but both in man and in the 
lower animals the large dose usually, though not always, accelerates 
the breathing, through a direct influence on the respiratory centres. 

Researches upon the effect of atropine upon the respiratory movement of air 
have been made by H. C. Wood, Heubach, E. Orlowski, E. Vollmer, and Unverricht . 
The experiments of Heubach, Orlowski, Vollmer, and Unverricht were made upon 
animals under the influence of morphine; H. C. Wood's experiments were upon 
normal, morphinized, and chloralized dogs. The first effect of atropine in the nor- 
mal animal is greatly to increase the respiratory air-movement. This primary 
excitement is usually soon followed by a decrease, which is not, however, sufficient 
to overcome the first rise; so that the air-movement remains for a long time dis- 
tinctly above the normal. In the chloralized dog the effect of atropine in increas- 
ing air-movements is constant and pronounced. In H. C. Wood's experiments 
(two in number), as also in Orlowski's and Unverricht's, with animals under the 
influence of opium, no increase, but rather a decrease, in the air-movement was the 
result of injections of atropine. In Heubach's and in Vollmer's experiments, which 
were numerous, atropine distinctly increased the air-movement in the morphinized 
dog. The action of opium upon the respiration in the dog is at present so little 
understood that the question of the contra-action of atropine and morphine is 
entirely apart from that of the action of atropine. There is also reason for believing 
that the toxic dose of atropine paralyzes the peripheral pneumogastric nerve in the 
lungs, since in profound atropine-poisoning no marked influence is exerted upon 
the respiratory rhythm by section of the pneumogastric. 

In Reichert's experiments it was found that if a dose two or three times the 
minimum lethal dose was given internally to the dog, the animal could be kept 
alive for hours b}' artificial respiration and ultimately recover. During the period 
of recovery certain remarkable phenomena habitually recurred, for an account of 
which the reader is referred to Reichert's article. 



DELIRIFACIENTS 101 

Glands. — Atropine lessens the secretion of probably all the glandu- 
lar structures of the body except the kidney and possibly the intes- 
tinal glands. Its effects are especially marked upon the salivary, 
mammary and sweat glands. It is generally believed that the diminu- 
tion in secretion is due to a paralysis of the peripheral ends of the 
nerves of the glands, since Keuchel has shown that stimulation of the 
chorda tympani fails to excite the flow of saliva, while irritation of 
the sympathetic will cause secretion. Mathews, however, combats 
this theory, and believes that the action of atropine is upon the gland- 
structure, asserting that nerve paralysis will not prevent secretion. 

Small doses of atropine sometimes, but not always, increase the 
How of urine. After the toxic dose the urine may be at first augmented, 
but is usually lessened very early, and may finally be entirely sup- 
pressed.* The assertion of Meuriot, that the urinary secretion rises 
and falls in atropine-poisoning with the arterial pressure, is not in 
accord with the results obtained by Walti, who found atropine to 
produce in the rabbit, independently of its action upon the circulation, 
a steady lessening in the urinary secretion. Harley affirms that 
medicinal doses of atropine decidedly increase the solids of the urine, 
slightly the urea and uric acid, very markedly the phosphates and 
the sulphates. 

Our knowledge of the action of atropine upon the secretions of 
the intestinal canal is very imperfect. It has been a matter of tra- 
ditional and clinical belief that the secretions are increased, and 
Harley gives some experiments which he asserts corroborate this; 
Meuriot, on the other hand, states that they are lessened. We cannot 
find, how r ever, any experiments that seem to us decisive; and clinical 
evidence certainly indicates that the intestinal secretions, if affected 
at all, are increased. 

Temperature. — In moderate doses atropine causes a pronounced 
rise in temperature, but in very large decidedly toxic amounts it 
lessens animal heat. Thus, in the dog, Meuriot has obtained an 
augmentation of from 1° to 3° C, and Dumeril, Demarquay, and 
Lecomte of 4° C. In fatal poisoning of the same animal, these observ- 
ers have noticed a fall respectively of 5.10° and 3° C. In man, Meuriot, 
in the use of medicinal doses, has observed the temperature to rise 
0.5° to 1.1° C, and Eulenburg 0.5° to 0.8° C. According to I. Ott 
and C. Collmar, this increase is independent of the blood-pressure, 
occurring both when the pressure is elevated and when it is depressed, 
and is accompanied by a greater increase of heat-production than 
of heat-dissipation. It is therefore due to the increased heat-produc- 
tion, which is the result, in all probability, of an influence upon the 
nerve-centres. Ott and Collmar believe that this influence is a stimu- 
lation of the thermo-genetic centres in the spinal cord, and that the 
rise of temperature is paralleled by that which occurs in tetanus. 
It seems to us more probable that it is due to paralysis of thermo- 

* See case of Gross (loc. cit,), also of Morer (Ann. Soc. de Med. de Gand, 1873). 



102 



GENERAL REMEDIES 



genetic inhibition. The final fall of temperature in atropine-poisoning 
is probably, at least in part, caused by the vaso-motor paralysis. 
Eye. — In all animals except birds,* atropine causes mydriasis with 
paralysis of accommodation and probably lessening intra-ocular 
pressure. The dilatation of the pupil appears to be due to the paralysis 
of the peripheral terminations of the oculo-motor nerve with probably 
a simultaneous stimulation of the sympathetic nerve supplying the 
radiating fibres of the iris. 

That the action of atropine upon the pupil is a local one is shown by the fol- 
lowing facts: When instilled into one eye it causes dilatation of the pupil only on 
the side to which it is instilled; it is capable of dilating the pupil after section of 
both the trigeminus within the skull and the sympathetic within the neck; f and 



Oc.M. 




Fig. 8. — Diagram of the Innervation of the Pupil. 

O. C. — Oculo-motor centre. Oc. M. — Oculo-motor nerve. Op. G. — Ophthalmic ganglion with 
nerve running to sphincter fibres of the pupils. D. C. — Dilator (sympathetic) centre iu the medulla. 
S. G. G. — Superior cervical ganglion. G. G. — Gasserian ganglion. L. C. M. — Long ciliary nerve 
running to radiating fibres of pupil. Atropine paralyzes the terminals of the oculo-motor nerve in 
the sphincter fibres and stimulates the endings of the sympathetic nerve in the radiating fibres. 
Cocaine stimulates the sympathetic endings. 

in the frog atropine will produce dilatation of the pupil after removal of the 
eye from the body (I. Koppe, Y. Valentin). According to Borelli mydriasis is 
produced by the alkaloid when applied to the eye of a man just dead. 

The dilatation induced by the local application of atropine is not due to a direct 
action of the drug upon the muscular fibres of the iris; for as all of these, both the 
radiating and the circular, are of the same nature (non-striated in mammals), their 
antagonism is simply due to position; and it seems inconceivable that mere posi- 
tion should affect the relations between a muscle and a drug. Moreover, Bernstein 



* The statement first made by Wharton Jones, that the reason atropine does not dilate the 
pupils of birds is that their irides have no radiating fibres, has been disproved by the beautiful 
anatomical researches of Alex. Ivanoff and Alex. Kollett (confirmed by Johannes Diegel). Although 
Donders say* that the pupillary action of atropine "is slight in birds, in which it was formerly 
overlooked," in our own experiments the most thorough application of very strong solutions to 
the eyes of pigeons has had no distinct effect. According to the experiments of Szpilman and 
Luchsinger, lack of action of atropine is probably due to the muscular fibres of the irides of birds 
being non-striated. In the oesophagus of the bird the muscle is non-striated, and atropine paralyzes 
it; in the oesophagus of the rabbit the muscle is striated, and atropine has no action; in the cat a 
portion of the oesophagus has smooth muscular fibres, a part striated, and the former is paralyzed, 
the latter unaffected, by atropine. 

t That this holds true for man has been shown by II. C. Wood, who, having an opportunity 
afforded him to give atropine hypodermically to a man whose eye had been severed from all 
communication with the nerve-centres, found that the pupil was still dilated by the drug. 



DELIRIFACIHNTS 



103 



and Dogiel (confirmed by Rossbach and Frtthlich and by 0. Englehardt) found that 
while galvanic irritation of the oculo-motor Derve was unable to cause contraction 
of the pupil in the atropinized eye, yet when the electrodes were applied to the 
eyes in such a way as to affect directly the iris, contraction occurred, — phenomena 
explainable only by the theory that the nerve-endings were paralyzed, while the 
muscle was unaffected. 

That the oculo-motor nerve is paralyzed is also shown by the fact that further 
dilatation of the pupil is caused by atropine after section of the cervical sympa- 
thetic. H. C. Wood has seen this effect in man after paralysis of the sympathetic. 
Both Donders and Stellwag von Carion insist that the paralysis of accommodation is 
proof of paralysis of the oculo-motor nerve, and it seems to us they do so with truth. 

It is probable that the sympathetic or dilating nerve-fibres of the iris are 
stimulated. ' Claude Bernard and Lcmattre both have found that atropine-mydriasis 
occurs in animals after section of the oculo-motor, and we have seen it in cases of 
complete oculo-motor paralysis in man. 

Clinical experience certainly shows that the dilatation produced by a mydriatic 
is not merely a passive movement of relaxation, but is active, capable of tearing up 
inflammatory adhesions even when of some firmness. The facts that the dilatation 
that occurs after the destruction of the oculo-motor nerve in animals, is not at all 
equal to that produced by atropine, and, indeed, can be largely increased by the ac- 
tion of the drug, and that in the eye separated entirely from the nerve-centres (see 
above) atropine still causes a wide dilatation, necessitate the belief either that the 
alkaloid acts upon the sympathetic fibrillse or that the peripheral fibres of a nerve 
are in themselves nerve-centres, acting upon the muscle of themselves even when 
separated from their centres. It has been urged against the view here taken that 
even the widest artificial mydriasis is increased by galvanization of the sympathetic. 
De Ruiter states the contrary; but, since Griinhagen, Hirschmann, and Engel- 
hardt separately affirm as the result of personal experiment, the correctness of the 
asserted fact, it must be accepted. Granting its truth, we do not think it warrants 
the deduction, since it is conceivable that an agent may excite the peripheral fila- 
ments of a nerve greatly, and yet not to such a point that they will be incapable of 
further excitation. Schultz believes there is in his experiments no stimulation of 
the dilator fibres, because when the superior cervical ganglion is destroyed and time 
allowed for the degeneration of the peripheral nerve-fibres, atropine, while dilating 
both pupils, does not destroy their inequality. This does not, however, seem to us 
to prove Schultz's conclusion, for it may well be that it is the intramuscular endings 
of the sympathetic nerve which are stimulated rather than the sarcolemma of the 
muscles themselves, — a theory rendered more probable by the fact that Schultz 
found that pieces of the iris of a cat, when exposed to a five-per-cent. solution of 
atropine, did not lose their irritability. 

SUMMARY.— Atropine is a paralyzant to peripheral nerve termi- 
nals, affecting in this way the vagi, the motor nerves, the secretory 
nerves and, to a lesser extent, the sensory nerves. It is also a paraly- 
zant to inhibition (perhaps preceded by slight stimulation), affecting 
the cardiac, intestinal and spinal inhibitory mechanisms. It acts upon 
the brain to produce delirium, in the frog it causes a state of palsy 
followed by motor excitation. It raises the blood-pressure by increas- 
ing the heart rate and by stimulating the vaso-motor centres ; after 
large toxic doses there is a failure of the circulation. It is a respiratory 
stimulant but, after excessive quantities, may become depressant. It 
dilates the pupil probably by a conjoint paralysis of the oculo-motor 
terminals and stimulation of the sympathetic. It finally paralyzes non- 
striated muscles, although there is frequently a primary increase of 
peristalsis probably through removal of inhibition. It diminishes all 
secretions (except of the intestines and kidney) by an action on the 
nerves in the glands. 



104 GENERAL REMEDIES 

Therapeutics. — In practical medicine atropine is employed in 
direct conformity to its physiological action, so that its use is best 
discussed under the headings of the various indications to meet which 
it may be administered. 

To Relax Spasm. — As the powers of atropine to relax spasm depend 
on its influence upon the peripheral nerve-filaments and the muscle- 
tissue, it is evident that it is a practical remedy only in those cases 
in which the spasm is due to some local cause connected with a muscle 
or its supplying nerve; hence it has been found especially useful in 
rheumatic torticollis, in the violent contractures and spasms sometimes 
accompanying neuritis, and especially such as follow nerve-wounds. 
It is essential that the alkaloid be injected directly into the contracted 
muscle, so as to get its concentrated influence upon the affected nerve 
and muscle, little or no relief usually being produced by so small an 
amount of the remedy as would reach the diseased part after absorption 
through the blood. 

The non-striated muscles are more affected by the atropine than 
the striated, and consequently the drug is found to be more efficacious 
in spasm of the involuntary than of the voluntary muscles. It is 
serviceable in lead colic, in simple spasmodic colic, in spasmodic dys- 
menorrhea, in spasmodic constriction of the bowels with obstinate 
constipation, in laryngismus stridulus, in nervous cough, in asthma, 
in hiccough, and in whooping-cough, in which last disease, as originally 
advised by Bretonneau, it has been largely used; also, even in the 
spasms accompanying the passage of renal and biliary calculi, where 
of course it usually fails. Wherever it is possible, it should be used 
locally in spasm of the involuntary as well as of the voluntary muscles. 
Thus, in spasm of the urethra, the ointment should be rubbed in along 
the canal; in rigid os uteri, the extract should be applied directly 
to the os; in asthma, belladonna should be inhaled, by means either 
of the cigarette or of the atomization of a decoction of the leaves; 
in spasm of the sphincter ani from fissure or other cause, it should 
be applied directly to the part by poultice or ointment. Under the 
present indication may be considered the use of the remedy in consti- 
pation. In doses of one-quarter to one-half grain (0.016-0.03 Gm.) 
of the extract, belladonna is of great service as an addition to laxative 
pills. In that form of incontinence of urine in children in which the 
real cause is an irritability of the bladder, so that spasmodic con- 
traction occurs under the stimulus of a small portion of urine, the 
continuous use of large doses of atropine is often of great service by 
reducing the irritability of the walls of the bladder, with which, 
owing to the method of its excretion, the alkaloid is brought in 
local contact. 

To Impress the Heart and Blood-Vessels . — In certain diseases, such 
as pneumonia, congestion of the lungs, etc., in which the local affection 
is closely connected with dilatation of the blood-vessels, Harley has 
highly commended atropine as a vaso-motor contractant. In most 
of these affections, however, the remedy has failed to establish itself. 



DELIRIFACIENTS 106 

As a stimulant to the circulation, belladonna has probably not 
been employed as much as it ought. Graves, however, commends 
it especially when the pupil is contracted in typhus fever, and it has 
been used with asserted advantage in erysipelas, scarlet fever, etc. 
In cases of sudden collapse occurring in acute disease and marked 
by falling of the temperature below normal, with great loss of the 
arterial tension and free sweating, atropine is of the greatest value. 
Such collapse is not infrequent in young children in the advanced 
stages of pneumonia, pleurisy, or other pulmonic disease, and is also 
prone to happen in puerperal mania and similar maniacal states 
occurring in exhausted patients. It is similar in its character to that 
which is produced by perforations of the stomach or intestine or as 
the result of surgical or accidental traumatisms. It is a condition of 
shock in which the loss of temperature is chiefly the result of vaso- 
motor paralysis. Proper treatment of this condition consists chiefly 
in the free use of external heat and the hypodermic injection of 
atropine, strychnine, and the tincture of digitalis; in many of these 
cases alcoholic stimulants are worse than useless. 

To Arrest Secretion. — In mercurial salivation atropine arrests almost 
at once the discharge of saliva, and seemingly facilitates greatly the 
return to health. In colliquative sweats, as originally recommended 
by Da Costa, it is probably the most valuable known remedy. One- 
eightieth to one-sixtieth of a grain (0.8 to 1.0 Milligm.) of atropine 
used hypodermically, at bedtime, will very frequently prevent the 
usual night-sweat. In colliquative diarrhcea it has been recommended 
by M. Delpage, and very probably will be found of service. Inunctions 
of the breast with belladonna ointment are habitually employed for 
the purpose of arresting the secretion of milk, and in the experiments 
of Hammerbacher upon a goat, atropine given internally lessened the 
secretion, especially of the watery portions of milk. It is largely 
employed to check excessive nasal secretions as in acute coryza or 
hay fever. 

To Stimulate Respiration. — It is stated that as far back as 1570 
it was affirmed that opium and belladonna are, in their influence upon 
the system, antagonistic. But the two drugs are in no wide sense 
really antagonistic. Atropine, is, however, a valuable remedy in 
opium-poisoning as a respiratory stimulant. In protracted opium- 
narcosis the cardiac and vaso-motor actions of atropine are of service; 
but it should never be forgotten that the main influence for good is 
upon the respiratory centres. As in overdose it becomes depressant, 
not more than one-fiftieth of a grain should be given. 

Whenever there is failure of respiration in other poisonings or 
diseases than that of opium, atropine in conjunction with strychnine 
is useful. It has been especially commended as an antidote to 
poisonous fungi.* 

* Atropine antagonizes the action of muscarine (the alkaloid of many of the poisonous mush- 
rooms) on the cardiac inhibitors as well as on the respiration. 



106 GENERAL REMEDIES 

As a Local Sedative. — Locally and freely applied, belladonna is a 
sedative, and, we believe, to glandular as well as to muscular and 
nervous tissues. In this way it is often very useful in various local 
inflammations. In the form of a plaster it is frequently employed to 
relieve neuralgic and rheumatic pains with very doubtful benefit. 
The ointment is sometimes of service in painful hemorrhoids. In 
mastitis, its local application to the breast is often very efficacious. 
Whenever belladonna is used locally, in order to get its good effects 
it must be employed freely. At the same time, it should be remem- 
bered that a number of cases of poisoning by its external application 
have been reported.* In children it must be used with caution; in 
adults, with a reasonable amount of care, its external use is safe, 
provided directions be given to have it washed off so soon as any 
affection of the sight or dryness of the throat is induced. 

Ophthalmic Uses.-\ — The instillation of a four grains to the ounce 
solution of atropine sulphate into the eye is followed in about fifteen 
minutes by dilatation of the pupil, usually reaching its maximum 
in from twenty-five to thirty-five minutes, and lasting until the 
third day. In about twenty-five minutes the power of accommodation 
begins to be lost, and in from an hour and a half to two hours is 
usually fully annulled: return begins on the second day, but the 
function may not be fully regained for over a week. 

Atropine is used by ophthalmologists: First, to dilate the pupil 
for purposes of ophthalmoscopy and to expose the lens in cases of 
incipient cataract so that all portions of it may be carefully examined, 
but is inferior in this respect to more rapidly and fugacious acting 
mydriatics, particularly a four-per-cent. solution of cocaine, a one- 
and a half-per-cent. solution of homatropine, or a ten-per-cent. 
solution of euphthalmine. Second, in iritis and irido-cyclitis to give 
rest to the iris and to prevent the development of synechia and 
occlusion of the pupil area with exudates; for this purpose it is the 
best of the mydriatics. Third, to paralyze accommodation when it 
is desired to determine with accuracy the refraction of the eye for 
the fitting of spectacles and other purposes, and to overcome spasm 
of accommodation; in such cases repeated instillations of the atropine 
solution may be necessary. Fourth, to give rest to the eye, to exert 
an anodyne alterative influence, and to lessen the liability to iritis in 
various forms of keratitis and ulcers of the cornea; in phlyctenular 
keratitis it is especially useful, and in perforating ulcers, particularly 
if they have a central situation, it overcomes the prolapse of the 
iris; for this purpose it must be used very freely. 

The existence of glaucoma, or any tendency to it, is a contra- 
indication to the use of atropine. It may in chronic glaucoma 
precipitate an acute attack, and in acute glaucoma causes marked 
increase of pain, of congestion, and of the already excessive 
intra-ocular tension. 

* See M. T. G., Nov. 1856 and London Pharm. Journ., 1871. 

t For this section the authors are indebted to Professor George E. de Schweinitz. 



DELIRIFACIENTS 107 

Administration. — For nearly till purposes for which tho drugs 
arc useful atropine sulphate is preferable to the various preparations 
of belladonna, stramonium or scopola, on account of the better 
absorption and more accurate dosage. When, however, the local 
action on the intestines is wished the slower absorption of the extract 
of belladonna makes it the preparation of choice. 

In dropping an atropine solution in the eye for local effect the head 
should be so inclined that the fluid will run out of the outer canthus, 
while pressure may be applied upon the optic end of the lachrymal 
duct to prevent passage of the solution into the mouth. Poisoning 
through the local use of the remedy by ophthalmic surgeons has 
often occurred. 

Toxicology. — The earliest symptoms of atropine-poisoning are 
a dryness of the throat and mouth with redness of the fauces, dilated 
pupil, disordered vision and possibly diplopia. The pulse is exces- 
sively rapid, and hard; the skin is warm and dry, and frequently 
an erythematous rash appears on the face and neck and sometimes 
spreading over the body. This eruption resembles that of scarlet 
fever, but lacks the punctation and is usually not followed by desqua- 
mation. Early in the poisoning there may be forcible expulsion of 
urine, but later there is commonly retention. The most striking 
symptom in a well-developed case is the peculiar talkative wakeful 
delirium, sometimes associated with hallucinations or illusions. Thus, 
we have seen a lady remain for a long time, holding fast to the bed- 
post, to which she talked in the most voluble manner as though it 
was an intelligent living entity. Sometimes the delirium is wild and 
the patient almost uncontrollably violent. Respirations are at first 
increased in both rate and depth but after very large doses may 
become slow and shallow, death if it occurs being immediately due to 
asphyxia. In cases of fatal poisoning, stupor and muscular paralysis 
finally develop, sometimes preceded by convulsions. 

The diagnosis, if in doubt, may be confirmed by instilling a few 
drops of the urine into the eye of a cat or other animal, when if the 
case is atropine-poisoning the pupil will be dilated. While this phys- 
iological test furnishes sufficient evidence for a working diagnosis it 
merely proves that the poisoning is by some mydriatic substance, 
not necessarily atropine. Morel calls attention to a sort of laryngitis 
produced by poisonous doses of belladonna, characterized by pain 
in the larynx, roughness of voice, and the expectoration of minute, 
pearly, tough pellets. It was present in the advanced stages of two 
cases of poisoning under his care. Raphael has noted glycosuria as 
a symptom of belladonna-poisoning and has experimentally produced 
the condition with atropine in rabbits. 

The minimum fatal doses of belladonna preparations are not known. 

An enema representing eighty grains of the root has produced death in five 
hours; * but, on the other hand, recovery has occurred after the ingestion of three 

* IP. G. H., Feb. 1845. 



108 GENERAL REMEDIES 

drachms of the extract.* A tenth, or even a twentieth, of a grain of atropine will 
often produce alarming symptoms; yet Chambers reports recovery in a child four 
years old who had taken about two teaspoonfuLs of a solution containing a grain 
of the alkaloid in half an ounce, and Stracham in a child of five years from a 
table-spoonful of glycerin containing one-half per cent, of alkaloids. 

Congestion of the lungs and of the membranes, and even of the 
substance of the brain and cord, may be found after death, and, 
according to M. Lemattre, congestion of the retina is an almost 
characteristic lesion. 

In the treatment of belladonna-poisoning, the stomach should be 
emptied by means of emetics or the stomach-pump. The best anti- 
dote is probably the compound solution of iodine in doses of six 
minims, as recommended by Prescott; in the absence of this, tannic 
acid in twenty-grain doses may be given. The various symptoms 
must then be met as they arise, respiration and circulation being 
maintained as in other narcotic poisoning; according to Reichert, 
recovery may follow after a dose much larger than the maximal 
fatal quantity if artificial respiration be persisted in. The exact 
value of opium in belladonna-poisoning has not been determined, 
and its employment should be tentative, although good is to be 
expected from its judicious use. Physostigmine and pilocarpine appear 
to be somewhat antagonistic to atropine within certain limits, and 
pilocarpine has been used in atropine-poisoning. (See Physostigma 
and Pilocarpus.) After toxic doses of belladonna, there is generally 
complete retention of urine; and as this secretion contains the greater 
part of the ingested poison, and as reabsorption from the bladder is at 
least conceivable, the catheter should be used early. 

HYOSCINE. 

Hyoscine is defined by the Pharmacopoeia as "an alkaloid chemi- 
cally identical with scopolamine, obtained from hyoscyamus and 
other plants of the Solanaceae." While to-day there is no longer any 
difference of opinion as to the chemical identity of the substance 
known in Germany as scopolamine with that known in this country 
as hyoscine, there has been much difference of opinion as to the 
physiological identity of the two alkaloids. The experiments of 
the early investigators were so different in their results as to afford 
a certain amount of justification for the belief that the two substances 
were distinct in their effects. Recent investigations have, however, 
afforded the explanation of these differences. The alkaloid hyoscine 
has the power of rotating polarized light to the left; certain specimens, 
will be much more active in their rotatory power than other specimens, 
although indistinguishable by any of the ordinary chemical tests. 
The comparative action of a specimen of hyoscine which possessed 
a high grade of rotatory power and that which was devoid of it has 
been studied by Cushny and Peeble. These authors found that the 

* Taylor's Medical Jurisprudence, London, 1873, 432. 



DiaiRlFAClKNTS L09 

effect of the two isomers upon the central nervous system was indis- 
tinguishable, but thai the hcvo-rotatory hyoscinc was much more 
actively paralyzant to the inhibitory fibres of the heart and to the 
secretory nerves.* 

The terms hyoscine and scopolamine are applied, however, in- 
discriminately by manufacturers to alkaloids of all degrees of rotary 
power, nor does the Pharmacopoeia make any distinction. It must, 
therefore, be conceded that, as the terms are at present used, they 
an 1 completely synonymous ; that hyoscine and scopolamine are not 
only chemically but also physiologically and therapeutically identical. 

Official Preparations : 

Hyoscinse Hydrobromidum ^Jjr to ^ grain (0.3 to 0.8 Milligm.). 

Scopolamine Hydrobromidum . 2 J,j to A grain (0.3 to 0.8 Milligm.). 

Physiological Action. f — The effect of hyoscine upon the cir- 
culation is comparatively feeble. The differences which have been 
obtained by various experimenters, according to Cushny and Peebles, 
depend upon the variations in the degree of rotatory power of the 
alkaloid. With large doses of the lscvo-rotatory hyoscine there is a 
depression of the peripheral endings of the pneumogastric nerve with 
consequent increase in the pulse-rate, similar to that seen after atro- 
pine; with hyoscine of low rotatory power, however, there is little 
or no change in the rate of the pulse, except after very large doses. 
In neither case does there seem to be any marked change in the 
blood-pressure, although Kochmann finds that small doses produce 
a slight rise through stimulation of the vaso-motor centre, and H. C. 
Wood that large doses are slightly depressant to both the heart and 
vascular system. 

Nervous System. — In the higher mammals hyoscine acts as a depres- 
sant to the cerebrum. In man, if used in sufficient doses, it nearly 
always eventually produces sleep, although sometimes preceded by 
a mild degree of delirium. According to Kochmann the electrical 
irritation of the psycho-motor area is lessened by the drug, and there 
is no analgesia during the sleep. 

In the frog hyoscine causes a lessening of the reflex action, which 
H. C. Wood attributed to the depression of the motor side of the spinal 
cord but which Cushny and Peebles believe is a result of the depressant 
action upon the peripheral endings of the motor nerves. Parisot 
asserts that after large doses a stage of excitement follows the 
depression similar to that caused by atropine. 

Respiration. — According to both Wood and Kochmann hyoscine 
acts as a depi'essant to the respiration, although it requires compara- 
tively large doses to produce any marked alteration in this function. 
In fatal poisoning by the drug death is always due to asphyxia. In 

* Kessel (.4. I. P., xvi. 1) was, however, unable to detect any difference in the effects of three 
samples of scopolamine ranging in their rotatory power from to —14.7°. 

t It has not been thought necessary to discuss in detail the older investigations concerning 
the physiological effects of hyoscine as the differences between the polarizable and non-polarizable 
alkaloid was not then recognized. The most important papers are those of Wood, of Kochmann, 
of Claussens, and of Kobert. 



110 GENERAL RKMEDIES 

this connection it is interesting to note that in the dog, as in man, it 
is almost impossible to kill with a single dose of hyoscine; Kochmann 
has injected as much as seven and one-half grains (0.5 Gm.) into a 
small dog intravenously without destroying life. 

Secretions. — Upon the secretions hyoscine acts much like atropine, 
producing lessening in the saliva, and, according to Kochmann, also 
in the sweat and mucous secretions. In cases of human poisoning, 
however, the skin is usually covered with moisture. 

Pupil. — Upon the pupil hyoscine acts like atropine, a half of 
one-per-cent. solution rapidly paralyzing accommodation and dilating 
the pupil. It is said that it does not produce any irritation, and that 
its maximum effects are reached in one-third the time necessary 
for those of atropine, and are more permanent and less affected by 
eserine.* Gley and Rondeau have found that the mydriasis is not 
prevented by previous destruction of the cervical sympathetic in 
the rabbit, and that irritation of the sympathetic nerve will increase 
the dilatation. 

SUMMARY.— The dominant physiological action of hyoscine is 
upon the cerebral cortex, producing sleep often accompanied by a 
low delirium. It is also a centric depressant of respiration, and 
depresses, though somewhat feebly, the whole motor cord : upon the 
sexual centres it acts more powerfully. Its influence upon the cir- 
culation is very slight. On the mucous membrane and probably on 
the muscles of the throat it acts powerfully, suppressing secretion 
and interfering with function. 

Therapeutics. — Hyoscine is a valuable hypnotic in those forms 
of insomnia in which sleep is banished by a continual flow of thoughts 
or mental images passing through an excited brain; hence it is often 
very effective in the insomnia of delirium, of acute mania, or of other 
forms of insanity. In some cases of insanity with cerebral excitement 
most excellent results are produced by the administration every 
three to five hours of small doses that will calm without causing sleep. 
As an hypnotic the alkaloid lends itself very well to combinations, 
intensifying greatly the influence of morphine, chloral, trional, and 
other drugs of the class. In cases of severe kidney disease it would 
seem to be a safer hypnotic than is morphine, and as it has no sedative 
influence upon the heart, it may be used when the feeble condition 
of that viscus forbids chloral. 

The use of enormous doses (one-fiftieth to one-twentieth of a 
grain) of hyoscine as a curative remedy in acute insanity has been 
advocated by H. R. Costons, and a remarkable case is recorded by 
Balagopal, in which one-sixth of a grain was given hypodermically 
to a patient suffering from violent, acute mania. Immediately after 
the injection the patient fell, crying that he was dying; his face 
became deadly pale, the conjunctiva insensitive, the breathing 
difficult and stertorous, the limbs spasmodically contracted. After 



* John Tweedy, Lancet, Dec. 18S6. 



DELIRIFACIENTS 111 

recovery, which occurred without remedies other than hypodermic 
injections of ether, the patient's mental condition rapidly improved, 
and in a week he was well. 

Probably through its influence upon the spinal centres hyoscinc 
is useful in all cases of sexual excitement, such as nymphomania, 
spermatorrhoea, and allied affections. It is the most certain remedy 
that we have in ordinary cases of over-frequent seminal emissions, 
which can usually be controlled by the administration of the one- 
hundred-and-twentieth to one-eightieth of a grain on going to bed. 

As an analgesic hyoscine is of little value, though Winnett states 
that it is very serviceable in the crises of locomotor ataxia. It has been 
used to a considerable extent in certain spasmodic disorders. Edlesen, 
as early as 1881, affirmed its value in asthma and whooping-cough. 
Erb has used it with advantage in various spasms. In spinal accessory 
spasm it has, in our hands, failed. On the other hand, in pronounced 
paralysis agitans, attended by much aching pain, we have seen it 
give very great relief from both pain and tremors. Usually in these 
cases it should be administered only at bedtime, as it is merely a 
palliative, and if used continually is prone to lose its power. 

In 1900 Schneiderlin suggested the hypodermic injections of large 
doses of morphine and scopolamine for the production of surgical 
anesthesia. In this method doses ranging from one-sixth to one-half 
grain of morphine in conjunction with from one-hundredth to one- 
fiftieth grain of hyoscine are injected an hour before the operation. 
The idea was founded on an erroneous conception of the physiological 
action of hyoscine, which is in no proper sense the antagonist of mor- 
phine and possesses but feeble analgesic properties. H. C. Wood, 
Jr., collected the reports of nearly 2000 cases, with 9 deaths, giving 
the frightful mortality of 1:221. Moreover in 69 percent, of the 
cases ether or chloroform was required to produce sufficient anes- 
thesia for operation. It is possible that in certain classes of cases the 
method may occasionally prove of value, but as a routine measure it 
cannot be too strongly condemned. 

Administration. — The action of hyoscine given hypodermically 
is manifested inside of ten minutes, and lasts from six to eight hours. 
In severe excitement, especially that of violent insanity, the dose 
should be repeated every six or eight hours. The dose for hypodermic 
use is from the one-hundred-and-fiftieth to one-eightieth of a grain 
(0.6-0.8 milligramme). Excessive susceptibility to the action of 
hyoscine being a not infrequent idiosyncrasy, it is best to give at first 
amounts below the minimum dose here stated. The tastelessness of 
hyoscine makes it easy to administer to insane or other patients 
without their knowledge. 

Owing to its great influence upon the throat, hyoscine is strongly 
contraindicated in cases of acute disease of the throat. Thus, we have 
seen it, when given in violent anginose scarlatina with delirium, cause 
such rapid increase in the difficulty of respiration as to suggest that 
it played an important role in the production of the fatal asphyxia. 



112 GENERAL REMEDIES 

Toxicology. — The symptoms which are produced in man by 
decided doses of hyoscine are dryness of the mouth, flushing of the 
face, great sleepiness, associated in some cases with semi-delirious 
inutterings, and a feeling of giddiness like that of intoxication. The 
respirations are lessened in frequency and mydriasis is usually, but 
not always pronounced. After very large doses the symptoms men- 
tioned are more intense, the pupils dilated, the mouth and throat 
excessively dry, and the voice hoarse or even partially suppressed, 
probably from paralysis of the vocal cords. 

The pulse-rate is usually not much altered, very frequently being 
slower than normal but in other instances has been rapid. The 
respirations are slow and full, and are said by H. M. Wetherill to be 
sometimes Cheyne-Stokes. The face and the general surface of the 
body are suffused, muscular relaxation is pronounced, and loss of 
coordination usually very evident. The skin, so far from being 
abnormally dry, is commonly bathed in perspiration. Several observ- 
ers assert also that there is a rise of temperature. Sometimes the 
delirium is active, accompanied by visual hallucinations, and clonic 
convulsions with opisthotonos have been noted. Mairet and Com- 
bemale found that monkeys when poisoned by it gave evidences of 
the presence of hallucinations, such as are sometimes produced in 
man. No fatal case of poisoning by hyoscine is on record. 

H. A. Hutchinson took a quarter of a grain of an impure hyoscine: quiet 
coma with entire muscular relaxation was produced, and lasted eleven hours. The 
fiftieth of a grain has, however, several times caused very alarming symptoms, and 
much smaller dosos are affirmed to have produced serious effects (see Carey). 

O'Hara saw one-ninety-sixth of a grain administered hypodermically produce 
very severe disturbance, lasting for twenty-eight hours, with total lack of remem- 
brance of occurrences which took place during the seven hours following the 
injection; while Root asserts that one-three-hundredth of a grain given by the 
mouth produced violent poisoning, and even one-twelve-hundredth very pronounced 
symptoms. The dispensing of such minute quantities of a drug is so difficult that 
it is probable that more of the alkaloid was given than is alleged. 

Homatropine Hydrobromide. Homatropine Hydrobromidum. — 
Homatropine is an alkaloid artificially produced from tropine, the 
hydrobromide of which is preferred for practical use on account of its 
being stable and not hygroscopic. It is said to cause, when taken 
internally, symptoms similar to those caused by atropine,* except in 
regard to the circulation. The retardation of the pulse has been 
proved by Tweedy and Ringer, Beyer, and De Schweinitz and Hare 
to be, at least in part, the result of a direct action of the drug upon 
the heart-muscle or its contained ganglia, since in the frog and in 
the terrapin the application of homatropine hydrobromide to the 
exposed heart in situ reduces very greatly the number of the beats. 
In the dog injection of the alkaloid into the jugular vein is followed 
by a fall of as much as thirty or forty beats per minute, which De 

* Brown {Ann. of Ophtkalm., xv. 237) reports delirium following instillation of two drops of 
a two-per-cent. homatropine solution in each eye. 



DELIRIFACIENTS 



113 



Schweinitz and Bare believe to be in part due to stimulation of the 

vagi nerves, because section of the vagi causes a marked increase in 
the pulse-rate, "although not such a rise as would appear if the 
inhibitory apparatus was intact." De Schweinitz and Hare found 
that the fall of the pulse-rate was accompanied by a marked fall of 
the arterial pressure. Since the production of asphyxia was followed 
at this time by a pronounced rise in the arterial pressure, it would 
appear that the fall of pressure is not the result of a vaso-motor 
paralysis, but of the cardiac influence of the drug. 

It has been shown by the experiments of Tweedy and Ringer, 
confirmed by De Schweinitz and Hare, that homatropine produces 
in the frog a brief period of tetanus, followed by absolute muscular 
relaxation, with abolition of reflex and voluntary activity, followed 
in from six to eight hours, if the dose has been properly proportioned, 
by return of voluntary movements, associated with tetanic spasms 
of great intensity. The convulsive movements and the paralysis are, 
according to De Schweinitz and Hare, of spinal origin, as the nerve- 
trunks and muscles are not affected. The cause of death is centric 
respiratory paralysis. 

The influence of the alkaloid upon the eye is practically identical 
with that of atropine, except that it is somewhat more feeble and is 
much more temporary. The pupil begins to dilate in from seven to 
twenty minutes after the instillation of the drug, and accommodation 
fails in from forty to ninety minutes; in from one to seventy-two 
hours the recovery is complete. According to De Schweinitz, a solution 
of one in eighty is sufficiently strong to paralyze accommodation 
completely, provided it be dropped repeatedly into the eye. When 
it is desired simply to dilate the pupil for ophthalmoscopic examina- 
tions, a single application of a solution of four grains to the ounce 
suffices. Homatropine as a practical mydriatic has the advantage 
of fugaciousness of action, of being not at all irritant, and of being 
little prone to produce systemic disturbance. 

INDIAN CANNABIS. 



Cannabis Indica is the dried flowering tops of the female plants 
of Cannabis sativa, or hemp, grown in India. According to most 
modern botanists, the Indian plant is the same species as the familiar 
hemp plant cultivated in this country, as well as parts of Europe. 
H. C. Wood has shown that the American plant possesses the same 
physiological properties as that grown in India. In the East hemp 
and its educts are used as narcotic stimulants. Gunjah is the dried 
plant as sold in the bazaars of Calcutta for smoking. Churrhus, known 
in Egypt as hashish, is the resinous exudation with the epidermis, 
etc., scraped off the leaves. 

Indian Cannabis occurs in commerce in greenish brown compressed 
masses markedly coherent from the large amount of resinous exudate. 
It has a peculiar narcotic odor and bitterish and somewhat acrid taste. 



114 CKNERAL REMEDIES 

Various substances have been announced as the active prin- 
ciple of cannabis indica, — cannabin, cannabinon, tetano-cannabene, 
oxycannabin, cannabene, etc. Cannabinol of Wood, Spivey, and 
Easterfield is, according to Fraenkel, inert, and should be known as 
pseudocannabinol, the name cannabinol being retained for a distinct 
substance which he, Fraenkel, has isolated and found to be active. 

Official Preparations : 

Extractum Cannabis Indicae J to % grain (0.01-0.016 Gm.). 

Fluidextractum Cannabis Indica? 1 minim (0.06 C.c). 

Tinctura Cannabis Indicae (10 per cent.) . . . 10 to 20 minims (0.6-1.2 C.c). 

Physiological Action. — When given in full doses, cannabis indica 
produces a feeling of exhilaration, with a condition of revery, and a 
train of mental and nervous phenomena which varies very much 
according to the temperament or idiosyncrasies of the subject, and 
very probably also, to some extent, according to the nature of his 
surroundings. The sensations are generally spoken of as very pleasur- 
able; often beautiful visions float before the eyes, and a sense of 
ecstasy fills the whole being; sometimes the venereal appetites are 
greatly excited; sometimes loud laughter, constant giggling, and 
other indications of mirth are present. Some years since, in experi- 
menting with an extract made from the American plant, H. C. Wood 
took a large dose, and described the results as follows: 

"About half-past four p.m., September 23, I took most of the extract. No 
immediate symptoms were produced. About seven p.m. a professional call was 
requested, and, forgetting all about the hemp, I went out and saw my patient. 
While writing the prescription, I became perfectly oblivious to surrounding ob- 
jects, but went on writing, without any check to or deviation from the ordinary 
series of mental acts connected with the process, at least that I am aware of. When 
the recipe was finished, I suddenly recollected where I was, and, looking up, saw 
my patient sitting quietly before me. The conviction was irresistible that I had 
sat thus many minutes, perhaps hours, and directly the idea fastened itself that 
the hemp had commenced to act, and had thrown me into a trance-hke state of 
considerable duration, during which I had been stupidly sitting before my wonder- 
ing patient. I hastily arose and apologized for remaining so long, but was assured 
I had only been a very few minutes. About seven and a half p.m. I returned home. 
I was by this time quite excited, and the feeling of hilarity now rapidly increased. 
It was not a sensuous feeling, in the ordinary meaning of the term; it was not 
merely an intellectual excitation; it was a sort of bien-etre, — the very opposite to 
malaise. It did not come from without; it was not connected with any passion or 
sense. It was simply a feeling of inner joyousness; the heart seemed buoyant 
beyond all trouble; the whole system felt as though all sense of fatigue were for- 
ever banished; the mind gladly ran riot, free constantly to leap from one idea to 
another, apparently unbound from its ordinary laws. I was disposed to laugh; 
to make comic gestures; one very frequently recurrent fancy was to imitate with 
the arms the motions of a fiddler, and with the lips the tune he was supposed to be 
playing. There was nothing like wild delirium, nor any hallucinations that I remem- 
ber. At no time had I any visions, or at least any that I can now call to mind; but 
a person who was with me at that time states that once I raised my head and ex- 
claimed, 'Oh, the mountains! the mountains!' While I was performing the vari- 
ous antics already alluded to, I knew very well I was acting exceedingly foolishly, 
but could not control myself. I think it was about eight o'clock when I began to 
have a feeling of numbness in my limbs, also a sense of general uneasiness and un- 



DKLIRIFACIENTS 115 

rest, and a four lost 1 had taken an overdose. I now constantly walked about the 
house; my skin to myself was warm, in fact my whole surface felt flushed; my 
mouth and throat were very dry; my legs put on a strange, foreign feeling, as though 
i hey were no! a part of my body. I counted my pulse and found it one hundred 
and twenty, quite full and strong. A foreboding, an undefined, horrible fear, as 
of impending death, now commenced to creep over me; in haste I sent for medical 
aid. The curious sensations in my limbs increased. My legs felt as though they 
were waxen pillars beneath me. I remember feeling them with my hand and find- 
ing them, as 1 thought at least, very firm, the muscles all in a state of tonic con- 
traction. About eight o'clock I began to have marked 'spells,' — periods when all 
connection seemed to bo severed between the external world and myself. I might 
be said to have been unconscious during these times, in so far that I was oblivious 
to all external objects, but on coming out of one it was not a blank, dreamless void 
upon which I looked back, a mere empty space, but rather a period of active but 
aimless life. I do not think there was any connected thought in them; they appeared 
to be simply wild reveries, without any binding cord, — each a mere chaos of dis- 
jointed ideas. The mind seemed freed from all its ordinary laws of association, so 
that it passed from idea to idea, as it were, perfectly at random. The duration of 
these spells to me was very great, although they really lasted but from a few seconds 
to a minute or two. Indeed, I now entirely lost my power of measuring time. 
Seconds were hours; minutes were days; hours were infinite. Still, I was perfectly 
conscious during the intermissions between the paroxysms. I would look at my 
watch, and then after an hour or two, as I thought, would look again and find that 
scarcely five minutes had elapsed. I would gaze at its face in deep disgust, the 
minute-hand seemingly motionless, as though graven in the face itself; the laggard 
second-hand moving slowly, so slowly. It appeared a hopeless task to watch during 
its whole infinite roimd of a minute, and always would I give up in despair before the 
sixty seconds had elapsed. Occasionally, when my mind was most lucid, there was 
in it a sort of duplex action in regard to the duration of time. I would think to 
myself, it has been so long since a certain event, — an hour, for example, since the 
doctor came; and then reason would say, No, it has been only a few minutes; your 
thoughts or feelings are caused by the hemp. Nevertheless, I w r as not able to shake 
off this sense of the almost indefinite prolongation of time, even for a minute. The 
paroxysms already alluded to were not accompanied -by muscular relaxation. About 
a quarter before nine o'clock, I was standing at the door, anxiously watching for 
the doctor, and when the spells would come on I would remain standing, leaning 
slightly, perhaps, against the door-way. After a while I saw a man approaching, 
whom I took to be the doctor. The sounds of his steps told me he was walking 
very rapidly, and he was under a gas-lamp, not more than one-fourth of a square 
distant, yet he appeared a vast distance away, and a corresponding time approach- 
ing. This was the only occasion on which I noticed an exaggeration of distance; 
in the room it was not perceptible. My extremities now began to grow cold, and I 
went into the house. I do not remember further, until I was aroused by the doctor 
shaking or calling me. Then intellection seemed pretty good. I narrated what I 
had done and suffered, and told the doctor my opinion was that an emetic was 
indicated, both to remove any of the extract still remaining in my stomach, and 
also to arouse the nervous system. I further suggested our going into the office, 
as more suitable than the parlor, where we then were. There was at this time a very 
marked sense of numbness in my limbs, and what the doctor said was a hard pinch 
produced no pain. When I attempted to walk up-stairs, my legs seemed as though 
their lower halves were made of lead. After this there were no new symptoms, 
only an intensifying of those already mentioned. The periods of unconsciousness 
became at once longer and more frequent, and during their absence intellection was 
more imperfect, although when thoroughly roused I thought I reasoned and judged 
clearly. The oppressive feeling of impending death became more intense. It was 
horrible. Each paroxysm would seem to have been the longest I had suffered; as 
I came out of it, a voice seemed constantly saying, 'You are getting worse; your 
paroxysms are growing longer and deeper; they will overmaster you; you will 



116 GENERAL REMEDIES 

die. ' A sense of personal antagonism between my will-power and myself, as affected 
by the drug, grew very strong. I felt as though my only chance was to struggle 
against these paroxysms, — that I must constantly arouse myself by an effort of 
will; and that effort was made with infinite toil and pain. I felt as if some evil 
spirit had control of the whole of me except the will-power, and was in determined 
conflict with that, the last citadel of my being. I have never experienced anything 
like the fearful sense of almost hopeless anguish and utter weariness which was 
upon me. Once or twice during a paroxysm I had what might be called nightmare 
sensations: I felt myself mounting upward, expanding, dilating, dissolving into the 
wide confines of space, overwhelmed by a horrible, rending, unutterable despair. 
Then, with tremendous effort, I seemed to shake this off, and to start up with the 
shuddering thought, Next time you will not be able to throw this off, and what 
then? Under the influence of an emetic I vomited freely, without nausea, and with- 
out much relief. About midnight, at the suggestion of the doctors, I went up-stairs 
to bed. My legs and feet seemed so heavy I could scarcely move them, and it was 
as much as I could do to walk with help. I have no recollection whatever of being 
undressed, but am told I went immediately to sleep. When I awoke, early in the 
morning, my mind was at first clear, but in a few minutes the paroxysms, similar to 
those of the evening, came on again, and recurred at more or less brief intervals 
until late in the afternoon. All of the day there was marked anesthesia of the skin. 
At no time were there any aphrodisiac feelings produced. There was a pronounced 
increase of the urinary secretion. There were no after-effects, such as nausea, 
headache, or constipation of the bowels. " 

The sense of prolongation of time present in most cases of hemp 
intoxication is evidently due to the immense rapidity of the succession 
of ideas. The mind measures time by the duration of its own processes, 
and when an infinitude of ideas arise before it in the time usually 
occupied by a few, time becomes infinitely prolonged to the mind. 
It is a lifetime in the minute. A very common mental phenomenon, 
not easily explained unless as a result of disassociation of the cerebral 
hemispheres, is a condition of double consciousness, a sense of having 
two existences, of being at the same time one's self and somebody else. 

In some cases Indian hemp produces, in addition to or even in the 
place of the symptom already spoken of, marked disturbances of 
motility. Convulsions have been noticed by Lawrie, and local spasms, 
with salaam convulsions, by F. H. Brown. According to O'Shaugh- 
nessy, the induction of catalepsy is not rare among the Hindoos. 

Whatever may be the symptoms of the first stage, sooner or 
later, if the dose be sufficient, drowsiness comes on. Generally, before 
it is marked, partial anesthesia, often with partial loss of strength, 
is manifested, especially in the lower limbs. The pupils are dilated, 
the pulse is quickened, and finally the subject falls into a heavy sleep, 
out of which he generally awakes hungry, without any of the wretched 
gastric sensations or the malaise felt after an opiate. Confusion of 
thought, however, may persist for some hours. Cannabis exerts no 
constipating influence upon the bowels, and appears to increase, 
rather than decrease, the excretion of the kidneys. 

In the dog, hemp extract causes exaltation followed by profound 
sleep (Hans Zeitler, H. A. Hare). That the drug has very little 
influence upon the vital functions is shown by the enormous amounts 
required to kill. Hare noted both in the dog and in the frog heightened, 



DKUHIKACIKNTS 117 

followed by markedly lessened, reflex activity. The loss of reflex 
activity was the result of an influence exerted upon the sensory side 
of the cord or upon the sensory nerve-trunk, the anesthesia in the 
frog being complete at a time when voluntary movement was pre- 
served; further, when the drug was applied directly to the nerve- 
trunk it produced sensory palsy. Although probably a local anesthetic, 
cannabis indica is too irritant to be applied to delicate mucous 
membranes. 

Therapeutics. — Hemp has been used in this country chiefly 
for the relief of pain, but also to some extent as an hypnotic. As an 
analgesic, it is very much inferior to opium, but may be tried when 
the latter is for any reason contraindicated. In full doses, in neuralgic 
pains, it certainly often gives relief. It has been very largely em- 
ployed to induce euthanasia in the advanced stages of phthisis, and 
constitutes, it is said, a popular nostrum employed for that purpose. 
In tetanus, Indian hemp has been used quite largely, and is sometimes 
apparently an aid to other remedies; it should be given to intoxication. 
As first suggested by Seguin, hemp extract, administered for months 
continuously in such doses as will keep just within the limit of distinct 
physiological effects, is often effective in migraine. 

Administration. — Extract of hemp is a very unsatisfactory drug 
from the fact that one-eighth of a grain of one extract will produce 
decided intoxication, and many grains can be taken of another extract 
that cannot be distinguished physically or chemically from the first 
specimen. The only way of using it with advantage is for the prac- 
titioner to try various samples in ascending doses, and use those which 
are active in the dose which he has found to be effective. The foreign 
extracts are, on the whole, more reliable than those made in America. 
It should always be borne in mind that, though the symptoms may 
seem alarming, there is much less danger in intoxication from hemp 
than from alcohol. No cases of fatal poisoning have been recorded. 
Notwithstanding the assertions of Fronmuller and Hiller, the tannate 
of cannabene of Merck has in our trials of it seemed to be inert. 

COCA. 

Two varieties of Coca leaves are recognized by the U. S. Pharma- 
copoeia, those derived from the Erythroxylon coca (known as Huanuco 
or Bolivian Coca) and those from the E. truxillense (Truxillo or 
Peruvian Coca). Both of these shrubs are natives of South America 
and are cultivated to a large extent, especially on the slopes of the 
Andes. The annual output is estimated at eighty million pounds, 
most of which is consumed in South America. 

Coca leaves are one to two inches in length, elliptical or oval in 
shape, not dentate and are distinguished from other medicinal leaves 
by a slightly curved line, running from the base to the apex, on each 
side of the midrib, and produced by the peculiar folding of the leaf 
in the bud. 



118 GENERAL REMEDIES 

Their odor, especially of the Truxillo variety, resembles that of 
tea leaves, the taste is bitterish and leaves a peculiar numbness in 
the mouth and lips. Coca depends for its activity on the presence of 
cocaine, of which alkaloid it contains about one-half of one per cent. 
Cocaine occurs in colorless, transparent prisms, soluble in six hundred 
parts of water, and forms with the acids very bitter, soluble, crystal- 
lizable salts. By prolonged boiling it is decomposed into methyl 
alcohol, benzoic acid and a substance known as ecgonine. Besides 
cocaine, the leaves contain a peculiar tannin, known as coca-tannic acid. 

Official Preparations : 

Fluidextractum Cocae \ to 2 fluidrachms (2-8 C.c). 

Vinum Cocae (6 J per cent.) \ to 1 fluidounce (15-30 C.c). 

Cocaina \ to \ grain (0.016-0.03 Gra.). 

Cocainae Hydrocldoridum \ to \ grain (0.016-0.03 Gm.). 

Oleatum Cocainae (5 per cent.) External use. 

Local Action. — Locally applied, cocaine acts as a very distinct 
and certain anesthetic, as was noted by Moreno y Maiz in 1862, and 
by Von Anrep in 1880, although it was not until September, 1884, 
that Karl Roller demonstrated the practical value of the drug. Accord- 
ing to the observations of Von Anrep, the nerves of special sense are 
as readily affected as are those of common sensibility: thus, cocaine 
placed upon the tongue abolishes at the place of contact, for the time 
being, the sense of taste. At the point of contact there is at first 
marked pallor, but after a short time very pronounced redness. In 
sensitive membranes like the conjunctiva, cocaine also causes at 
first much pain. The primary pallor is alleged to be due to a very 
powerful constriction of the small blood-vessels, and has led F. H. 
Bosworth to the conclusion that cocaine produces rigid contraction 
in unstriped muscular fibres whenever it comes in contact with them. 
The anesthesia is not, however, due to any spasm of the vessels, but 
to a direct action upon the nerve-trunk. Applied to the bared nerve, 
cocaine paralyzes first the sensitive and afterwards the motor fibres 
(Feinberg). Arloing asserts that the concentrated solution of cocaine 
placed on the bared nerve produces a distinct organic change in the 
nerve. 

According to the experiments of Peter Albertoni and of B. Dan- 
ilewsky, cocaine in sufficient concentration acts upon all forms of 
protoplasm, first exciting and then paralyzing functional activity. 

Absorption and Elimination. — The soluble salts of cocaine are 
absorbed with great rapidity. They have the power of passing with 
almost equal ease through all mucous membranes, so that their absorp- 
tion is almost immediate when they are employed locally in the nose, 
urethra, or other part; hence the large number of serious poisonings 
which have resulted from their local use. The ultimate fate of cocaine 
in the body is at present somewhat uncertain. It appears to escape 
to some extent through the urine unchanged (Thomas Moreno y 
Maiz and others), but the amount that has been recovered by chemists 
has been so small (five per cent., Wiechowski) as to lead to the wide- 



DELIRIFACIENTS 119 

spread belief that the alkaloid is in great part destroyed in the system; 
Glasenap believes I hat he has found ecgonine, a decomposition product, 
in the urine. 

Physiological Action. — From the days of the Incas the leaves 
of the coca plant have been enormously used by the natives of Western 
South America as a stimulant. Mixed with ashes or a little lime, 
they are chewed, and are said to increase greatly for the time being 
the muscular strength and endurance. Moderate doses appear to 
increase temporarily, to a very extraordinary degree, both physical 
and mental power. Various travellers concur in praising the peculiar 
sense of calm and happiness, the insensibility to fatigue, and the 
increase of bodily and mental activity which the drug produces. 

Montegazza slates that when he took two hundred grains of the leaves he was 
in a short time plunged into a condition of peculiar delirious beatitude, in which 
he seemed to be isolated from the rest of the world and to live in a peculiar atmos- 
phere of active calm. In a little while there came also a sense of plenitude of power 
which was accompanied by a real increase of physical ability, so that gymnastics 
which in his ordinary condition were impossible to him became easy. This state 
was succeeded by a natural profound sleep, lasting sometimes for twenty-four hours. 

Thus, on one occasion Montegazza took thirty-five grammes, and an hour later 
nine grammes, etc., until he had taken in the course of two hours sixty grammes in 
all. The heart, which after the earliest dose had been slow in its action, directly 
after the second dose suddenly became rapid and very violent in its beats; but 
at the end of the two hours the palpitations had ceased, although the pulse was 
still 128 per minute. There was now a condition of intoxication similar to that 
which is produced by hashish. Montegazza was possessed by a feeling of intense 
beatitude and inner joyousness, while a succession of visions and phantasmagoria, 
most brilliant in color and form, trooped rapidly before his eyes. He rapidly passed 
into a delirious condition, in which he appeared to himself to be unconscious, al- 
though when addressed he would answer rationally. An hour or two later he was 
sufficiently calm to say to his friends "that God was unjust, in that He had made 
man to live without eating coca. I prefer a life of ten years of coca to one of a 
thousand years without it. " As this state was passing off, he was seized with an 
almost irresistible desire to reproduce its delirium by taking more coca. Finally, 
however, he fell into a condition of sleep, which lasted only three hours. After this 
he was able to resume at once his ordinary occupations, and offered no physical 
evidence of his coca debauch. 

Pronounced aphrodisiac properties have been attributed to coca, 
but they seem to rest upon tradition rather than upon demonstrated 
experience. According to M. Unanne, the ancient inhabitants of 
Peru represented Venus by a female figure with a coca-leaf in her 
hand, and the coca still plays an important part in the nuptial 
ceremonies of the Indians. 

It has been affirmed by Tschudy and Unanne that coca is able to 
take the place of food; but this is clearly not the case. Weddell 
himself states that although an Indian chewing the coca could go on 
foot many hours without fatigue and without food, yet at the end he 
would eat more at one repast than he himself would take in two days. 
He accords with Bibra in stating that coca has the power of putting 
aside for some time the sense of hunger. While, however, it may 
mask the appetite, it certainly does not nourish the body, and it is 



120 GENERAL REMEDIES 

indeed most probable that the absence of hunger is the outcome of a 
local benumbing of the gastric nerves. Thomas Moreno y Maiz made 
several crucial experiments b} r keeping animals in pairs without food, 
and giving to one coca freely. These experiments have been repeated 
by B. von Anrep, and in every case the animal which received the coca 
died at least as early as its mate. 

Very small doses (one- to three-one-hundredths of a grain of cocaine) produce 
in the frog no other symptoms than some evidences of excitement. After doses 
of from one-tenth to one-fiftieth of a grain the frog becomes quiet, with an apparent 
increase, however, in the reflex activity, sometimes amounting to tetanus, fol- 
lowed by increasing palsy and failure of the respiration; very large doses produce 
symptoms of paralysis. 

In the domestic animals the symptoms vary. In the rabbit there is first a pecul- 
iar state of quiet, followed in a few moments by a condition of great excitement, 
in which the animal springs and jumps about. A few minutes later the rabbit again 
becomes quiet, and now, although trembling much, is so weak that he moves with 
difficulty. The tremblings increase until they merge in convulsive movements of 
the legs, while at the same time there is partial paraplegia; pendulum movements 
of the head are very marked, and finally epileptiform convulsions appear, while 
simultaneously a peculiar tetanic rigidity seems to indicate spinal excitement. The 
lethal dose for a rabbit is put at a grain and a half per kilo. Dogs and cats are 
said to be more susceptible to the action of cocaine than is the rabbit, and to suffer 
similar symptoms, but especially with the dog the evidences of mental excitement 
are more pronounced. 

According to Von Anrep, after an injection of cocaine the dog will dance and 
leap, never standing still for a moment, and continually circling around the experi- 
menter. The movements are not at all those of convulsions, but voluntary, and 
accompanied by every expression of joy and exhilaration. This may continue 
for hours, the animal then becoming gradually quiet, and passing finally into his 
normal condition. If instead of a moderate dose a toxic one has been given, there 
is first a period in which the animal is veiy restless but seems full of terror and 
anxiety; the least sound frightens him, causing him to tremble and to drop his tail 
between his legs. He does not appear at this time to know his master. Rhyth- 
mical movements of almost all portions of the body accompany this state. Fifteen 
or twenty minutes later the mental condition alters, and the dog becomes appar- 
ently full of joyous excitement. He barks loudly, runs from one person to another, 
licking them, and giving all the characteristic signs of joy. After a few moments 
this condition gives way to one of increasing feebleness; the dog gradually becomes 
unable to move, rhythmical movements, cramps, and convulsive symptoms appear; 
the pendulum-like swinging of the head gets very violent, and at last narcosis, 
with epileptiform convulsions, develops. It is evident that many of these symptoms 
are psychical. 

Nervous System. — Moderate doses of cocaine apparently act as a 
stimulant to the whole central nervous system. The effect upon the 
brain is shown by the increase of intellectual activity as well as by 
the stimulation of the psycho-motor area. The reflexes are exag- 
gerated through the stimulant influence of the drug upon the spinal 
cord. After large doses convulsions ma}' occur which may be in 
part of cerebral origin but are certainly also due at least in part to 
the excitation of the cord. X After toxic doses there occurs a secondary 
depression of the spinal cord. In the frog cocaine is capable of causing 
a paralysis of both sensory and motor nerves, but in the mammal 
such effect can be brought out only by the local application, on account 



DELIRIFACIKNTS L21 

of the powerful influence of the drug upon the respiration, Its action 

upon the sensory nerves is distinctly more powerful than its effect 
upon the motor nerves. 

L. Dadd states that distinct histological changes can be recognized in the cells 
of the nerve-centres as the residt of poisoning with cocaine, and that these lesions 
arc most marked in the cerebral cortex. 

B. von Anrep believes thai the drug has a very distinct and peculiar influence 
upon the semieirciilar canals, thereby causing the peculiar pendulum-like motions 
of the head, the lack of coordination, and the rolling convuLsions especially seen 
in doves. 

According to the researches of Von Anrep, the convulsive movements are of 
cerebral origin, and are arrested by section of the spinal cord; but the experiments 
of L. I. Tumass indicate that they do not arise in the psycho-motor centres of the 
brain-cortex, since he found not only that the local application of cocaine lessens 
the irritability of these centres, but also that during the convulsive stage of cocaine- 
poisoning the centres are less sensitive than normal. Danini, moreover, appears 
to have found that section of the cord does not prevent convulsions in the hind 
feet, and the experiments of Mosso show that when the upper cord iscut in the dog 
and the animal cocainized, the irritation of the nerve-trunk or of the surface will 
produce in a little while general muscular rigidity. Both Mosso and Von Anrep 
are in accord with other observers in stating that reflex activity is at first increased 
by cocaine. The motor paralysis and the loss of reflex activity which finally occur 
in cocaine-poisoning are probably in part the result of an influence upon the nerves; 
but that they are chiefly due to a direct sedative action upon the spinal cord seems 
to follow from the experiments of Mosso, who found that when he so bound the 
hind legs of the frog as to prevent the access of cocaine to the nerves, there was a 
rapid loss of reflex activity, and indeed a complete paralysis, at a time when both 
the motor and the sensory nerves were still intact. 

An observation made at a certain stage of the poisoning by Dr. Ott — viz., 
that irritation of the posterior column of the spinal cord produced no effect, while 
a prick of the anterior column was followed by the usual result — indicates that 
there is the same difference in action upon the sensory and motor tracts as upon 
the corresponding nerve-trunks; but Mosso's experiments upon tritons led him to 
conclude that the power of conducting impulses efferently, or from the centre, is 
first lost in the spinal cord poisoned with cocaine. 

Almost all observers agree that the sensory nerves after sufficient doses are 
finally paralyzed in cocaine-poisoning; but Mosso believes that the respiratory 
centre is more susceptible to the action of cocaine than are the sensory nerves, 
and certainly doses of the alkaloid not dangerous to life have no perceptible general 
effect upon the sensory nerves of mammals. The experiments of Nikolsky, of B. 
von Anrep, of Ott, and of Laffont seem to prove that the sensory paralysis is preceded 
by increased functional activity, which is in accord with the observation of Mosso, 
that in doses of 0.05 to 0.1 gramme cocaine increases in man the sensibility of the skin. 

According to Danini, the motor nerves in the frog remain irritable until after 
death; but, according to Nikolsky, their functional activity is first increased and 
afterwards destroyed. Ott, Mosso, and Popielski agree that cocaine depresses the 
motor nerves. Moreno y Maiz found that when he tied the iliac artery of a frog 
on one side and administered cocaine anteriorly, there came a time when irritation 
of the poisoned limb caused no movement, while irritation of the protected extrem- 
ity provoked very distinct general reflexes; at the same time there was dimin- 
ished motility in the non-protected limb as compared with the protected one: facts 
which, of course, indicate that the drug finally depresses both motor and sensory 
fibres, but that its action upon the motor is subordinate to that upon the sensory 
nerves. H. Alms found that a five-per-cent. solution of cocaine in contact with 
the isolated ischiatic plexus of the frog caused absolute anesthesia of the leg and 
apparent loss of motor power, the leg lying motionless and trailing behind. Never- 
theless, strong irritation upon the front leg of the frog caused immediate move- 



/ : 



122 GENERAL REMEDIES 

ments which were shared by the cocainized hind leg, showing that the motor fila- 
ments were not paralyzed. The experiments of Alms indicate that the extreme 
peripheral filaments of the nerve are first affected, since at a certain period most 
severe irritation of the skin produced no pain in the poisoned rabbit, although the 
injection of irritating materials evidently caused violent pain. 

According to Verebely and Horvath, the action of cocaine upon the nerve- 
endings is so pronounced that demonstrable changes can be noted after it has been 
applied locally. 

Circulation. — The action of cocaine upon the circulation is in 
some details so complex that in spite of much work it is not yet fully 
understood, but in the main our knowledge concerning it is clear. 
It produces a rise in pressure which is chiefly due to the stimulation 
of the vaso-motor centre in the medulla, although there is some evi- 
dence that the heart is also stimulated. The vaso-motor spasm as 
shown by the blanching of mucous membranes after its topical appli- 
cation is probably a purely local action. There is no convincing 
evidence that when given internally it has any direct action upon 
the arterial muscles. Concerning the pulse-rate, there is much diver- 
gence of statement. According to Reichert, a very small dose of 
cocaine decreases the rate by stimulation of the cardio-inhibitory 
centre, moderate doses increase the rate by depressing these centres 
and in some cases also the intrinsic inhibitory mechanism, while large 
doses may finally slow the heart by the action upon the motor ganglia. 

The experiments of Danini, of Berthold, and of Reichert are concordant in 
showing that after section of the spinal cord alone, or of the spinal cord and the 
vagi, cocaine does not distinctly increase the arterial pressure, — proof that the 
chief cause of the rise of the arterial pressure under the influence of cocaine is centric 
vaso-motor spasm. 

As showing the stimulant action of the small dose of cocaine on the heart, 
Mosso and H. G. Beyer, as the result of their experimental studies, made in the one 
case on the cut-out frog's heart, in the other upon the isolated heart of the terrapin, 
found that the minute dose of the alkaloid increased the whole amount of force 
put out by the heart, as well as the power of the individual systolic contraction; 
while Pachon and Moulinier, in experiments with cocaine on the heart of the frog 
in situ, find that after a moderate dose of cocaine there is a hypertonicity of the heart 
due to a direct action upon the muscular fibres. Observers affirm that the heart 
of the mammal is arrested by the toxic dose in diastole, which is in accord with the 
statements of Von Anrep and Nikolsky concerning the heart of the frog and of H. G. 
Beyer concerning that of the terrapin, diastolic arrest being affirmed by all these 
investigators. Pachon and Moulinier declare that the ventricles are arrested in 
systole, the auricles in diastole. According to these investigators, the arrhythmia of 
advanced cocaine-poisoning is really a rhythm which differs from the normal in 
that the contractions occur in regular groups; later there is a dissociation of the 
auricular and ventricular rhythms. 

The action on the vessels is uncertain. Mosso found that when he experi- 
mented with artificial circulation upon extirpated kidneys small doses of cocaine 
had no sensible effect upon the blood-vessels; and Durdufi states that marked 
narrowing of the vessels of the rabbit's ear can be seen when cocaine is injected, 
but is prevented by previous section of the sympathetic. Contrariwise, H. G. Beyer 
found in experiments upon the terrapin that both large and small doses of cocaine 
produce contraction of the blood-vessels by a direct influence; and Laffont experi- 
mentally reached the conclusion that one of the chief actions of cocaine is to contract 
the blood-vessels by affecting the nerve-endings in their walls. 






DKUKIFACIKXTS 123 

The results of the studies made by various investigators with t ho direct appli- 
cation of cocaine to the heart lead to the conclusion that while small doses of the 
alkaloid feebly stimulate the Viscus, toxic doses act as a depressant and finally as 
a paralyzant; thai cardiac depression is one of the causes of low arterial pressure 
in advanced cocaine-poisoning is further evidenced by the rapid and immediate 
fall in the pressure which occurs when cocaine is injected into a dog whose spinal 
coid has been cut and vaso-niotor system paralyzed.* The opinion of Reichcrt, 
that widening of the blood-paths by vaso-motor paralysis is the most important 
factor in the causation of lowered blood-pressure in advanced cocaine-poisoning, 
seems to be so far correct that the probabilities are that such widening of the 
blood-pat lis occurs. 

The testimony as to the action of the alkaloid upon the pulse-rate and upon 
the inhibitory nerves of the heart is so various that no positive conclusions are 
warranted without further study. 

Von Anrep states that the pulse-rate is usually increased, but that this increase 
is not marked in rabbits, while in Ott's experiments upon dogs the pulse usually 
becomes slower. Von Anrep also states that the vagi are paralyzed by large doses 
of cocaine, while Ott, Nikolsky, Laffont, and Durdufi declare that it does not affect 
the vagi, and Berthold states that previous section of the vagi has no effect upon 
the course of the symptoms caused by cocaine. 

Rcichert found in an elaborate series of studies that "very small doses of 
cocaine decrease the rate by stimulating the cardio-inhibitory centres; small to 
moderate doses increase the rate by depressing these centres, and in some cases by 
depressing also the cardio-inhibitory ganglion; large doses cause a transient 
decrease, followed by a rise or a permanent decrease, the decrease being due to a 
depression of the accelerator or motor ganglion in the heart, and the increase to the 
factors before mentioned. The cardio-inhibitory centres are invariably affected, 
being primarily stimulated and secondarily depressed. " 

Muscles. — Although there is some contradiction of evidence, yet 
it would appear established that cocaine is a direct muscle poison, 
at first stimulating and in large doses afterwards paralyzing. These 
effects are, however, probably too slight to be demonstrable in warm- 
blooded animals. 

Alms, Nikolsky, and B. von Anrep state that the striated muscles are not 
affected by the alkaloid, while Ott affirms that it acts upon them like veratrine 
and is confirmed in this by Buchheim and Eisenmenger. The tracings given by Ott 
would appear to prove that the muscular contraction is prolonged by cocaine, and 
can hardly be accounted for by a condition which M. J. Rossbach and B. von Anrep 
allege to be produced, — viz., a peculiar sensibility of the muscle similar to that 
produced by curare, and, like it, caused by a lessening of muscle-tonus by paralysis 
of the peripheral nerve-endings. 

In the ergographic experiments of Benedicenti cocaine both heightened muscular 
energy and increased resistance to fatigue, f while Mosso found that in man, when 
the muscles were exhausted by work and fasting, the exhibition of cocaine in the 
dose of a grain and a half more than doubled the response to stimuli. These experi- 
ments throw a peculiar light upon the assertions of travellers, that cocaine in the 
South American Indians enormously increases the power of withstanding fatigue. 
The present difficulty in the way of the full acceptance of the natural deductions 
from them is the fact that in America and in Europe cocaine has appeared to fail 
as a stimulant during fatiguing labors. 

Temperature. — The rise of rectal temperature in cocaine-poisoning 
sometimes amounts to as much as 8° F. It is certainly not due to the 

* See experiments of I. Ott, Toxicological Studies, 1874, 30. 

t Sobieranski believes, however, that the effect of cocaine is through the nerve-centres (see 
Gazetta Lekarska, 1896, No. 4). 



124 GENERAL REMEDIES 

convulsions, as it usually occurs before the motor disturbance.* In 
fatal cases it is followed by a fall, so that before death the temperature 
may become subnormal. In the calorimetrical experiments of Reichert 
the rise of temperature was found to be due to a great increase in the 
heat production. 

Reichert has further determined that after section of the spinal 
cordf at its junction with the medulla, as well as after section of the 
crura cerebri, cocaine is powerless to produce rise of the temperature, 
and therefore concludes that the rise of temperature produced by 
cocaine is of cerebral origin, and is due to stimulation of the thermo- 
genic centres in the caudate nucleus and to motor excitement produced 
by stimulation of the cortical motor centres. 

Urinary Secretion. — Such varying results have been recorded by 
clinicians as to the effect of cocaine upon the amount of urinary 
secretion that its action is probably not constant. According to 
Bignon, the single large dose may produce an anuria so prolonged as 
to bring on uremic symptoms. There is some reason for believing 
that cocaine reduces the nitrogenous elimination, but the experi- 
ments upon the subject are hardly sufficient to warrant the positive 
conclusion that the alkaloid checks protoplasmic waste. 

I. Ott and Atherton P. Mason have found that when cocaine is taken habit- 
ually it not only lessens the urinary secretion but also markedly decreases the 
elimination of urea, while in three experiments Richard Fleischer determined that 
the alkaloid markedly reduces nitrogenous elimination. Mason experimented with 
very large therapeutic doses of cocaine taken during prolonged exercise, and states 
that his results were contrary to those previously reached by Gazeau. 

In Ott's experiments the urine, under the influence of cocaine, became full of 
calcium oxalates. Sugar and albumin have been frequently noted in the urine 
of poisoned animals, but Von Anrep affirms that their presence is due to the 
prolonged asphyxia induced by the drug. 

Eye. — When locally applied about the eye cocaine produces a 
dilatation of the pupil which from a four-per-cent. solution reaches 
its maximum in about an hour and disappears in from twelve to 
twenty-four hours. The dilated pupil is to some extent responsive 
to light and accommodation and can be further dilated by atropine 
or contracted by physostigmine. 

The dilatation is certainly due at least in part, perhaps solely, to 
the stimulation of the sympathetic (dilator) nerve-endings. The fact 
that physostigmine is capable of contracting the pupil would indicate 
that the oculo-motor system is not entirely paralyzed, and the increase 
in dilatation produced by atropine suggests also the same conclusion. 

The experiments of Nikolsky, Holtzke, Limbourg, as well as of SchQler and 
Pfliiger (quoted by Limbourg), show that cocaine applied to the eye immediately 
after section of the sympathetic does dilate the pupil, although later, when suffi- 

* P. Langlois and Charles Richet have found that the temperature of the cocainized animal 
has a great effect in determining the amount of cocaine necessary to produce convulsions. The 
higher the temperature the smaller the dose necessary, and when the animal was kept at a 
temperature of 39° C, only tonic convulsions were produced. 

t The rise of temperature which has been noted by Mosso after section of the spinal cord may 
have been the result of imperfect division. 



DELIRIFACIENTS 125 

dent time has elapsed for degeneration of the sympathetic fibres (<> occur, the 

alkaloid is powerless. This would appear to prove I hat cocaine dilates the pupil by 
Stimulating the sympathetic ncrvc-cndin^s; hut, according to Schultz, very strong 
solutions of cocaine will dilate the pupil after nerve degeneration has occurred, 
though weaker solutions fail to act. Further, Schultz found that when, in the 
cat, he extirpated the superior cervical ganglion on one side, waited a sufficient 
length of time for degeneration of the dilator nerves, and then applied cocaine to 
both eyes, he obtained a maximal dilatation on the unoperated side, but a medium 
dilatation on the operated side. Allowing the correctness of Schultz's experiments, 
the double action of cocaine appears to be demonstrated. Limbourg states that. 
electrical irritation of the cornea may restore to such an eye the power of 
responding to cocaine. 

Respiration. — Small doses of cocaine increase distinctly the rapidity 
of the respiration, and in some cases also the depth (Von Anrep, Mosso, 
Danini, Ott, and Nikolsky). After toxic doses the respirations become 
at first rapid and more shallow, then irregular with interruptions, 
after each of which the respiratory movements begin deep and slow, 
but become more rapid and shallow until the next stand-still. As 
Mosso found that after section of the vagi cocaine causes an enormous 
increase of the rapidity of the breathing and at the same time so 
modifies the rhythm that expiration is no longer quicker than inspira- 
tion, it must be considered that the drug acts directly upon the 
respiratory nerve-centres as a respiratory stimulant. The first 
stimulant effect of cocaine upon the respiratory centres appears to 
be followed after fatal doses by a paralyzing influence which leads to 
death from asphyxia. 

Intestines. — According to Von Anrep, the intestinal peristalsis is 
markedly increased by moderate doses. After large doses this increase 
is followed by great sluggishness deepening into paralysis. Tarchanoff 
states that coca increases the mucous secretions, but Von Anrep 
affirms that it decreases them.* 

SUMMARY. — Cocaine is a primary stimulant, and in toxic quanti- 
ties secondarily depressant to the brain and spinal cord Jv When 
locally applied it is a paralyzant to peripheral nerves, acting much 
more powerfully on sensory than on motor nerves, i In moderate 
doses it is stimulant, in overdose depressant, to the vaso-motor 
centres. Upon the heart itself the moderate dose of the alkaloid 
acts primarily as a stimulant, increasing to a slight extent the 
amount of force put forth by the heart ; in toxic quantities it lessens 
the heart action. There is also reason for believing that cocaine 
exerts a direct influence upon the coats of the blood-vessels, which 
is, however, so feeble as not to be of practical importance except 
when the cocaine is applied locally. Upon striated muscles cocaine 
appears to have a peculiar though very feeble action, which is not 
manifested during poisoning by it. Upon the eye cocaine acts as a 
mydriatic. It is a powerful stimulant to the respiratory centres, in- 
creasing the rapidity and fulness of the respirations, but if the dose 

* M. E. Gley states (Compt.-Rend. Soc. Biol., iii. 560) that when cocaine is injected into the 
portal vein it produces comparatively little effect, and he believes that it is destroyed in the liver. 
Phis i- criticised by Chouppe Uoiil.). 



126 GENERAL REMEDIES 

be sufficiently large it after a time causes the respirations to 
become very shallow, and finally paralyzes the respiratory cen- 
tres. Moderate doses are said to increase, large doses to paralyze, 
peristalsis. 

Therapeutics. — Locally cocaine is largely used for its anes- 
thetic influence (see page 51). It is also of value as a topical remedy 
by virtue of its action in constringing the blood-vessels. In acute 
coryza a ten-per-cent. solution applied to the nostrils will sometimes 
afford permanent relief, but a combination of a four-per-cent. solution 
with bismuth (three drachms to the ounce of mucilage) is more gen- 
erally useful. It should be applied by means of a dropper every 
three or four hours. In hay fever, in the peculiar irritated sore throat 
of advanced phthisis, in chronic laryngitis, in inflamed hemorrhoids, 
in fissure of the anus, and even in open cancer its application will often 
afford temporary relief. In some cases of dysentery with excessive 
nervous irritability of the rectum, cocaine suppositories are of great 
service. Cocaine is also sometimes useful as a local hemostatic in 
arresting nasal and other mucous membrane hemorrhages. 

For local use the two- to ten-per-cent. solution may be employed, 
care being exercised not to use a possibly fatal dose of the drug. 

As an internal medicament cocaine is useful as a respiratory 
and circulatory stimulant and as a tonic. It is largely used in the 
same class of cases in which strychnine is found to be available. Less 
powerful in its influence than is strychnine, it is especially useful 
as an aid to that alkaloid. (See Respiratory Stimulants.) Its stimulant 
influence upon the cerebrum naturally led to the expectation that it 
would be of value in cases of depression of spirits and even of true 
melancholia. The results of our own experience, after thorough trial, 
however, are in accord with the generally expressed opinions of 
alienists, that it has no remedial value in any form of mental aberra- 
tion. Sometimes it appears to produce at first a temporary relief, 
but this does not continue; and if the remedy be pushed, anorexia, 
restlessness, or other disagreeable symptoms usually demand its 
withdrawal. In neurasthenia and hysteria it is valuable only as a 
stimulant and stomachic, acting better in the form of the fluidextract 
than cocaine itself; and in all these cases there is especially the danger 
of the formation of the cocaine habit. Large doses of the fluidextract 
are sometimes of service. 

In the form of large doses of the fluidextract, coca has appeared 
to us to be of service during the breaking off of the opium habit, 
exerting some stimulant influence upon the nervous system, and 
restraining the tendency to diarrhoea and loss of appetite; care must 
be taken, however, not to substitute a new habit fully as pernicious 
as the old one. Some European clinicians have found cocaine of service 
in the treatment of serous diarrhoeas. It is undoubtedly of value for 
the relief of excessive vomiting, especially when due to gastric irritation. 
Thomas D. Dunn states that hypodermic injections of one grain 
control the pain of migraine. Aschenbraidt asserted that, in doses 



DKLIR1KAC1ENTS 127 

of 0.15 grain, cocaine was a valuable stimulant during forced marches; 
but in a series of careful trials with it by the medical rowing crew of 
the University of Pennsylvania it appeared to have no value, and the 
general experience seems to conform with this result. 

Toxicology. — The symptoms which have been present in 
cocaine-poisoning, or have been produced by the coca-leaf or its 
preparations, in the United States or in Europe, differ essentially 
from the descriptions of those said to be caused by the plant in the 
South American natives.* We believe that in no recorded cases has 
there been anything resembling the beatific visions and exhilarations 
described by Montegazza. Ordinarily, in the mildest cases of poisoning 
with us, there are great restlessness and nervous excitement, but no 
sense of beatitude; rather a condition of terror. With this state 
come usually distinctly accelerated pulse, increased frequency of 
respiration, and, perchance, muscular twitchings or even mild con- 
vulsions. In the more severe cases of poisoning the symptoms vary; 
sometimes there have been nausea, vomiting, rapid, almost imper- 
ceptible pulse, great perspiration, and collapse with or without loss 
of consciousness; in other cases the pulse has been slow and feeble, 
and sometimes pronounced cyanosis, with slow or almost arrested 
respiration, has been the most alarming manifestation. The pupils 
are usually dilated, but have been reported in some cases as "con- 
tracted." After very large doses convulsions usually occur; they 
are often violent and epileptiform; not rarely, at times, at least, 
they are partial, and in many cases opisthotonos has been pronounced. 
Consciousness rarely escapes; usually it is simply lost, but sometimes 
it is merged into a mania with hallucinations and delusions, which 
mania may become violent and even homicidal, as in a case reported 
by Mattison. 

The number of cases of poisoning by cocaine is very great, and 
although large doses have been recovered from, excessively violent 
symptoms have followed the use of smaller amounts. It is remark- 
able, also, that in many of these cases the drug has been employed 
for a local effect. 

The fatal cases, to the details of which we have had access, are those reported 
by Kolomnin, twenty-four grains into the rectum for local anesthesia; F. M. Thomas, 
four-per-cent. solution used locally for toothache, in unknown quantity; Knabe, 
four-per-cent. solution, twelve drops given hypodermically to a girl of eleven years, 
death in forty seconds (for details, see J. B. Mattison); J. H. C. Simes, one drachm 
of twenty-per-cent. solution injected into the urethra, followed immediately by 
violent convulsions, ending in death in twenty minutes, autopsy proved that ure- 
thra was not ruptured. Half an ounce of a two-per-cent. solution of cocaine injected 
into hydrocele and allowed to stay about a minute is said to have caused death 
(Paul Berger). O. H. Garland, death said to have been due to the application of 
twenty drops of a five-per-cent. solution to the gum. E. Phster, death from an 
unknown quantity of a twenty-per-cent. cocaine solution injected into the urethra. 

Some of the most remarkable cases of poisoning by small quantities are those 
reported by T. H. Burchard, ten drops of a four-per-cent. solution injected hypo- 

* The belief of H. H. Rusby, that these differences depend upon alterations of the coea-leaf 
during its drying and transmission across the seas, has hardly been sustained (Therap. Gaz., 1888). 



128 GENERAL REMEDIES 

dermically caused unconsciousness and apparent death in four minutes; Myer- 
hausen, eight drops of a two-per-eent. solution upon the conjunctiva produced in 
a girl of twelve years violent symptoms; George T. Stevens, one in which four 
minims of a three- and a half-per-cent. solution, given to a strong man, produced 
violent convulsions, followed by mania; Grosholz, three drops of a four-per-cent. 
solution in the eye; Frost, one drop of a one-per-cent. solution in the eye produced 
in a child of fourteen marked poisoning; Ramsden Wood reports violent poisoning 
with four minims of a t wenty-per-cent. solution. A number of cases are on record 
in which very severe symptoms have been produced by one grain given hypoder- 
mically (see Mattison, Addinsell, and Pitts); and it is plain that, although this 
dose has been used to a considerable extent, its employment is unjustifiable. The 
occasional effects of the local application of cocaine are very remarkable.* 

On the other hand, large amounts of the drug have been recovered from. 

Von Ploss reports twenty-two grains taken by an apothecary, by the stomach, 
with spontaneous recovery, although the urine was suppressed for twenty-four hours. 
In another case ten grains taken hypodermically in the course of five hours produced 
complete unconsciousness, excessive failure of circulation, slow respiration, recov- 
ery under treatment (J. S. Spear) ; E. Caldwell reports recovery after the hypodermic 
injection of five grains, which produced convulsions with asphyxia. A case reported 
by W. Finlay is interesting, because six grains given Irypodermically to a pregnant 
woman lowered the pulse to 38 and the breathing to 5, but did not cause a 
miscarriage. 

It is not safe to put upon mucous membranes amounts which if 
given hypodermically would be dangerous; so that not more than 
three-quarters of a grain should be used locally. 

The treatment of cocaine-poisoning must be largely symptomatic. 
When there is great cerebral and motor excitement, we have found 
chloroform to act very happily. Partial anesthesia may be main- 
tained for some moments. If the symptoms do not yield to such 
medication, chloral may be cautiously exhibited. When the toxic 
manifestations are syncopal, hypodermic injections of digitalis may 
be given, Avhile alcohol and ammonia are exhibited by the mouth. 
In some cases life has been apparently saved by artificial respiration. 
Intra venous injection of salt solution has been recommended, f 

Cases of cocainismus or chronic cocaine habit are not rare, but in 
the great majority of instances the victim is addicted to the use of 
more than one narcotic. Usually the cocaine has been taken as a 
substitute for, or aid to, morphine: in a number of cases the habit 
has been formed by the local use of the drug for hay fever. The 
symptoms are in no way characteristic; dreaminess, apparent inability 
to attend to the ordinary duties of life, loss of reliability, promptness, 
and punctuality, varying mental aberration suggesting, but different 
from, that of paranoia, occurring in any case, should arouse suspicion. 
The paranoiac, unless greatty depressed, is usually egotistical, self- 
reliant, conceited; the victim of cocainism. in matters not connected 
with his habit, is usually even less self-assertive and more easily led 

■ * In addition to cases mentioned, see Brit. Med. Journ., Nov. 1885; Deittsch.Med.Wochensch., 
No. 46 % 1886; New York Med. Rec, 1886, ii.; La Pratique Med.. Jan. 1891; S. J., eclvii. 201. 

t Systemic Lavage for Poisons. — Intravenous injection of normal saline solution as a treatment 
for acute poisoning has been experimented upon by Carlo Bozza (.Canadian Pract., 1898, xxiii.), 
who believes that it leads to rapid elimination and slow absorption, owing to fulness of the blood- 
vessels. He determined that the minimum fatal dose of cocaine given to dogs hypodermically is 
0.025 gramme per kilo; rising to 0.03 if hypodermoclysis is employed, and to 0.035 with lavage 
of the organism. 



DKLIR1FACIKNTS 



129 



than the normal individual. Magnam affirms that a peculiar hallu- 
cination as to the existence of foreign bodies under the skin is 
characteristic. 

The will and the desire to reform are as weak as in the opium habit, 
and the greatest difficulty is usually to get the victim earnestly to 
desire reformation. The abrupt withdrawal of the narcotic is proba- 
bly always safe; thus, in a case in which fifteen grains were taken 
hypodermically daily, the immediate cessation of exhibition was 
followed by no greater disturbance than diarrhoea, dyspepsia, and 
nervous depression, which subsided in the course of two or three days. 
(For cases, see Grundlach and Mattison.) 



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Ott and Collmar.T. G., Aug. 1887. 

Raphael D. M. W., 1899, xxv. 

Reichert P. M. J., Jan. 1901. 

Richter N. Cb., i. 294. 

Ringer Pract., March, IS 

1879, i. 474. 

ROLLETT A. Op., XV. 1. 

Rossbach and Frohlich. .Pharmak. 

such., Wurzburg, i. 

Schultz A. A. P., 1898. 

Shaw J N. M. D., vii. 27. 

Stracham L. L., 1901, i. 

Szpilman and Luchsinger ... .A. G. P., xxiv 

1881. 347. 
Unverricht B. K. W., 1896. 

9 



377; L. L., 



Untcr- 
6. 



Valentin. 



Vollmer . . . 
Von Carion. 



Walti 

Wiechowski 

Wood 

Wood 

Wood 

Wood, Jr. . . 
Zeller 



.Versuch einer physiol. Pa- 
thologie der Nerven, 
Leipsic, 1864, ii. 368. 

.A. E. P. P., xxx. 

.Der intraoculare Druck und 
die Innervations Verhalt- 
nisse der Iris, Vienna, 1868. 

.A. E. P. P., 1C95, xxxvi. 

.A. E. P. P., 1901, xlvi. 

.J. P., 1892. 

. P. M. T., i. 290. 

.A. J. M. S., April, 1873. 

.T. G., April 15, 1901. 

.V. A. P. A. lxvi. 384. 



HOMATROPINE. 

M. News, 1887, li. 



De Schweinitz and Hare. 
731. 

HYOSaNE. 

Balagopal Indian Med. Rec, 1894. 

Carey U. M. M., i. 

Claussens In. Dis. 1883. 

Cushny and Peeble. . J. P., 1905, xxxii. 501. 
Gley and Rondeau. .C. R. S. B., 1887 iv. 56. 

Hutchinson A. and N., iii. 539. 

Kobert A. E. P. P., 1887. 

Kochmann Ther. Geg., 1903, v. 202. 

Mairet and Combemale. .C. R. S. B., 1887. 

O'Hara T. G., ii. 

Parisot J. de P. P., 1906, viii. 823. 

Root T. G., ii. 

Wetherill T. G., i. 199. 

Winnett West. Med. Rev., 1898, iii. 

210. 

Wood T. G., Jan. 1885. 

Wood, Jr Amer. Med., 1905. 

CANNABIS 1NDICA. 

Fraenkel A. E. P. P., 1903, xlix. 

Hare T. G., 1887. 

Lawrie Stilld's Therap., i. 772. 

Wood Proc. Amer. Philosoph. Soc, 

1869, xi. 226. 
Zeitler In. Dis., 1885. 



Addinsell 

Albertoni. . . . 

Alms 

Arloing 

Ast henbraidt 
Benedicenti. . 

Berger 

Berthold. 



COCAINE. 

.Lancet, 1888, i. 
.A. G. P., 1890, xlviii. 
.A. Ph., 1886, Suppl. 
.Lvon M.j May, 1883. 
.D. M. W., 1883, ix. 50. 
.U. N. M. T., xvi. 170. 

B. M. S. C. P., 1891, xvii. 

C. M. W., 1885, 435. 



Beyer A. J. M. S., July, 1885. 



130 



GENERAL REMEDIES 



lilliKA. 



BlGNON. . . . 

bosworth . 
Caldwell 

I ) Mil' 

Danilewsky. 

Dl N N 

DrjRDUFI. . . 

eisenmenger. 
Fbinbebo. 

1'IM.AY. . . 

Garlanii. . 
Glasenap. 



Gbundlach. 

Koller 

LlMBOURG 

Magnam. . 



REFERENCES (Continued). 

.Die Narkot. Genuasmittel, Mason B. M. S. J., Sept. 1882. 

1855. Mattison Med. R., 1887, i. 

I. A. M. A., July. 1887. Moreno v Maiz . .Thesis, Paris, 1868. 

.N. Y. M. I; .. Nov. 15, 1884. Mosso A. G. P., 1890, 557. 

.B. M. J., 1885. Pachon and Moulinier. .C. R. S. B., 1898, v. 

L. B M 1899. Pfister B. K. W., 1896, xxxiii. 

A. (I. P., 1892, li. Pitts Lancet, 1887, ii. 

T. G., 1888. Popielski Cb. P., 1896, x. 

. L>. M. \\ '., 1887. 172. Reichert Am. Lan., May, 1891. 

Pflanzenstoffe, 2d ed., 885. Reichert P. M. J., i902. 

,B. K. W '.. March, 1887. Simes M.News, 1888. 

.Aus. M. Gaz., 1887, ii. Spear N. Y. M. R., 1885. 

. Lancet, Nov. 1895. Tumass A. E. P. P., xxii. 

.In. Dis., St. Petersburg, Verebely and Horvath. . .Cb. N., 1899, xviii. 

1894. Von Anrep A. G. P., 1880, xxi. 

.S. Jb., 1886, ccxii. Von Ploss Husemann's Pflanzenstoffe, 

.W. M. W., Nov. 1884. 2d ed. 

.A. E. P. P., xxx. Wiechowski A. E. P. P., 1901, xlvi. 

.N. C, 1896, 15. Wood Aus. M. Gaz., Aug. 1886. 



FAMILY V.— EXCITO-MOTORS. 



In this class are included such drugs as increase the reflex activity 
of the spinal centres, and thereby give rise to disturbance of motility. 
The only representatives of the class used by the practitioner of 
medicine are those drugs which contain strychnine as their active 
principle. 

NUX VOMICA. 

The seeds of Strychnos Nux-vomica, a middle-sized tree growing 
in the East Indies and Australia, whence the drug enters commerce. 
The fruit of the nux-vomica tree resembles externally the orange. 
Each fruit contains four or five seeds. These are circular, nearly 
flat disks, a little less than an inch in diameter, covered with very 
short, satin-like, grayish hairs; internally they are tough and horny, 
and are possessed of an intensely bitter taste. The effects of nux 
vomica are due chiefly to the alkaloid strychnine — of which it should 
contain not less than one and a quarter per cent., although it contains 
another alkaloid of physiological activity, brucine. These alkaloids 
exist in combination with an acid, the so-called igasuric of Pelletier 
and Caventou, which, according to Husemann, is identical with malic 
acid. It is usually estimated that strychnine constitutes about forty 
per cent, of the alkaloids. Practically there is no qualitative difference 
between the medical action of strychnine and that of the cruder 
preparations of nux vomica, over which it usually should have the 
preference on account of definiteness of action. 

As kept in the shops, strychnine is a grayish-white powder, but 
may be obtained in octahedral or quadrilateral prisms. It is so bitter 
that it will impart a very intense bitter taste to seven hundred thou- 
sand times its weight of water. On account of its insolubility (one 
in about three thousand parts of cold water) it is very rarely used in 
medicine, at least in the United States, the sulphate being universally 
preferred, and being what is commonly meant in American writings 
when the word "strychnine" is used. Strychnine sulphate contains 
about seventy-five per cent, of strychnine. 

Official Preparations : 

Extract um Nucis Vomicae (5 per cent, of 

Strychnine) \ to \ grain (0.015-0.03 Gin.). 

Fluidextractum Nucis Vomicae 1 to 3 minims (0.06-0.18 C.c). 

Tinctura Nucis Vomicae (0.1 per cent. 

Strychnine) 10 to 30 minims (0.6-2.0 C.c). 

Strychnina i/o to r<j g ra i n (1-3 Milligm.). 

Stryehninae Sulphas . . tsV *° uV g ra i n (1 _ 3 Milligm.). 

Strychnince Nitras ^ to fa grain (1-3 Milligm.). 

131 



132 GENERAL REMEDIES 

Local Action. — The local action of strychnine is that of a very 
feeble irritant; upon the mucous membrane of the stomach it acts 
like a simple bitter. 

Absorption and Elimination. — Strychnine is absorbed rapidly, 
whether taken by the mouth or by hypodermic injection. 

Several investigators have attempted to determine the comparative rate of 
absorption of strychnine in different portions of the alimentary canal by isolating 
these different portions by ligatures and then injecting strychnine into them. After 
tying the pylorus, Bouley and Colin found that the absorption of strychnine was 
rapid in the stomachs of dogs and cats, while Tappeiner determined that in cats it 
was taken up very slowly. In two series of experiments, S. J. Meltzer found that, 
after tying the cardiac and pyloric ends of the stomach, large doses of strychnine 
would remain in the stomach of the rabbit without producing any physiological 
effect, while under similar circumstances in the dog the gastric absorption was 
extremely slow and uncertain. It is rapidly absorbed in the small intestine. 

Strychnine has been detected by chemists in the blood, kidney, 
liver, heart, brain, spinal cord; indeed, practically in all portions 
of the system. The statement of R. W. Lovett, that it accumulates 
in the spinal cord, has been disproved by Ipsen and by Lesser. 

Strychnine is eliminated promptly, having been detected in the 
urine five minutes after its absorption, and others have detected it in 
the urine half an hour after its exhibition; and in various poisoning 
cases, fatal within two hours, it has been found in the urine. Kratter 
and Mann believe that they have proved that the elimination is 
complete within forty-eight hours.* It escapes from the body to 
some extent unchanged, as it has been found in the urine by Peter 
von Rautenfeld, by Wormley, by Schauenstein, and by Kratter. 
According to P. C. Plugge, a portion of the alkaloid is converted into 
strychnia acid.'f 

Physiological Action. — According to the experiments of Borzi, 
strychnine affects vegetable protoplasm. LTpon all animals strychnine 
probably acts similarly, but with great variations of power. 

According to Leube, it takes ten times as much strychnine to kill chickens 
as it does to kill other birds, weight for weight; and among mammals the guinea- 
pig is very insensitive to it. It has also been asserted that on some monkeys it has 
but little influence (Boston Med. and Surg. Journ., 1872). Very young animals 
are said to be quite insensitive to it. J The resistance of birds to the poison is 
attributed by Falck partially to slow absorption and partially to a destruction of 
the poison in the body. 

The characteristic symptom produced by the toxic dose of strych- 
nine is violent convulsion in which all the muscles of the body are 
involved, which may endure until death from asphyxia, the spasm 
of the muscle of the chest preventing respiration. We have seen 

* Schiff and Lautenbach believe that they have proved that the alkaloid is destroyed, at 
least in part, in the liver; a conclusion which is strongly combated by Chouppe and Pinet (Compl.- 
Rend. Soc. Biol., 1887, cv.), and is very doubtful. 

t The theory that strychnine becomes fixed in certain tissues of the body, originally proposed 
by Widal and Nobecourt, has received considerable credence, but its correctness has certainly not 
been proven. For discussion of the whole subject, with experiments and literature, see paper of 
S. J. Meltzer and G. Langmann. 

% See Arch. f. Ges. Physiol., 1884, xxiv. 530; also Behrend Lau {Elmshorn Inaug. Diss., 1886). 



EXCITO-MOTORS 133 

death occur in the first convulsion in animals; but Tardicu states 
that he knows of no such instance in man (compare case of Denime). 
After a time the paroxysm is at an end, the jaw drops, the muscles 
relax, and a period of calm comes on, to be succeeded by a second 
convulsion like the first. These convulsions are excited by the slight- 
est touch, by a draught or breath of air, even by a loud sound; but 
a firm grasp or hard rubbing of the muscles is frequently grateful. 
A slight rigidity is sometimes manifest between the paroxysms, but 
no marked stiffness. 

Cerebrum. — So far as our present knowledge goes, strychnine has 
little or no influence upon the cerebral cortical centres. The stimu- 
lation of the special senses sometimes seen in the beginning of strych- 
nine-poisoning is probably, though not certainly, peripheral in its 
origin; consciousness is probably never directly affected by the drug. 

Spinal Cord. — The spinal origin of the convulsions of strychnine 
was first demonstrated by Magendie in what was probably the earliest 
pharmacological study leading to the therapeutic use of a drug, and 
has been confirmed by a large number of experimenters. After the 
administration of the drug, even in doses too small to give rise to 
convulsions, the reflexes are greatly exaggerated. The spasms occur 
after section of the spinal cord below the point of division. 

It has been proved by Van Deen, by Valentin, and by A. J. Spence that when 
strychnine is placed upon the cut upper surface of the brain or spinal cord so that it 
will diffuse itself within the spinal cord without being carried by the circulation, 
convulsions appear in those muscles whose nerves have their origin near the point 
of application, and spread from muscle to muscle as the poison creeps through the 
cord. The accuracy of the statement of Claude Bernard, that when all the posterior 
nerve-roots are cut no convulsions occur, whereas, if a single afferent root remains, 
irritation of its nerve will cause general tetanic spasm, has been denied by Spitzka, 
but is probably correct. If so, it demonstrates that the reflex motor ganglionic 
cells are incapable of originating an impulse, and in strychnine-poisoning are simply 
in such a condition of over-excitability as renders them exceedingly sensitive to 
slight irritations and causes them to respond most energetically to the feeblest 
stimulus, the convulsion always being therefore a reflex phenomenon. 

Whether the action of the alkaloid is upon the sensory or upon motor ganglia 
of the spinal cord is not yet definitely proven. The observations of Spence would 
seem to indicate that it is the sensory apparatus which is excited. This investi- 
gator found that after its local application to the upper part of the spinal cord, as 
the poison travelled down the cord there was a time when irritation of the fore feet 
caused only spasm in them; later in the experiment, irritation of the front feet 
caused spasm of both the front and hind feet, although irritation of the latter did 
not produce other than normal reflex movements; later still in the poisoning came 
a stage when irritation of the front legs was powerless to cause spasm in the hind 
legs, although irritation of the latter would now cause spasm in the former. Bier- 
nacki believes that the cortical portion of the pyramidal or motor tract does not 
share in the stimulation, because he has found that in the strychnized rabbit the 
psycho-motor centres in the brain are even less susceptible to stimulation than 
in the normal animal. 

On the other hand evidence that the effect is on the motor apparatus is fur- 
nished by the experiments of Van Deen, who so divided all the tissues that the 
anterior portion of an eviscerated frog was connected with the posterior solely by 
the posterior columns of the cord. When one or two drops of a solution of strych- 
nine were placed in the mouth of the prepared batrachian, tetanus, confined to the 



134 GENERAL REMEDIES 

anterior segment of the body, was developed; and it was also found that while 
irritation of the posterior feet caused in them only ordinary reflex movements, in 
the front legs tetanic spasms were simultaneously induced. 

Strychnine is evidently a powerful stimulant to the motor cells of the whole 
spinal tract up to the pons Varolii. Hare found demonstrable histological changes 
in the cells of the anterior cornua. 

Motor Nerves. — After death from strychnine, the functions of 
the motor nerves are always found to be more or less impaired, so 
that galvanization of the nerve-trunk produces either very feeble 
contractions in the tributary muscles or none at all.* 

Although this paralysis of the motor nerves may be, in part, due 
to the exhaustion produced by the excessive number of violent 
impulses which travel along the motor nerves during the period of 
strychnic convulsions, the drug exercises a direct depressant action 
on the motor end plates. 

Kolliker found that when he cut the sciatic nerve in the frog and exhibited 
strychnine the divided nerve would respond to galvanic stimulation after all func- 
tional power had been lost in the nerve whose connection with the centres was 
intact. These experiments have been confirmed by Martin-Magron and Buisson, 
and must be accepted. On the other hand, it has been shown by Vulpian, by E. 
Poulson, by C. G. Sautesson, and others, that when the nerve has been divided, 
as in the experiments of Kolliker, it finally becomes paralyzed in strychnine-poison- 
ing; and Vulpian lias found that if the doses liave been properly adjusted the motor 
nerve after a time will regain in the poisoned frog its activity before stimulation 
of the spinal cord lias altogether passed off, so that the history of such an experi- 
ment is, first, tetanus, — then paralysis, due to the loss of power by the nerve-trunks, 
— and then again a tetanus which gradually subsides into the normal condition. 
Further, as pointed out by Richet, and as we have frequently seen, if an enormous 
dose of strychnine be injected into the jugular veins of the dog, death immediately 
results practically without convulsion. Under these circumstances the motor 
nerves will be found to have entirely lost their power of responding to galvanic or 
other stimulation, although they may still be able to transmit sufficient efferent 
impulses from the spinal cord to produce slight but distinct choreic muscular 
contractions. 

Sensory Nerves. — The afferent or sensory nerves appear not to be 
affected by strychnine. Martin-Magron and Buisson having tied all 
the tissues of a hind leg of a frog except the nerve, and injected 
strychnine into the body of the batrachian, found that at a time 
when convulsions had ceased in all portions of the body except the 
leg to whose nerve the poison had not had access, slight irritation of 
the poisoned foot would induce tetanic spasms in the protected leg, 
thus showing that though the motor nerves to which the strychnine 
had had access were completely paralyzed, the afferent nerves were 
still functionally active. 

* See Matteucci (Traite des Phenomenes clectro-physiologiques, Paris, 1841), Moreau (Comptes- 
Rendus Soc. de Biol., 1855), M. Ambrosoli (Gazette Mcdicale. 1857, 525), Wittich (Bericht d. Fort- 
schritte d. Anal., 1857, 434), Kolliker (Virchow's Archiv, 1856, x. 239), and Vulpian (Archives de 
Physiologie, Nov. 1870, 125). The statement of W. H. Klapp, that he has found in thirty-seven 
experiments the motor nerve unimpaired in the frog after death from strychnine (Journ. Merit. 
and Nerv. Dis., Oct. 1878), may depend upon the fact that in some species of frogs the nerves are 
extraordinarily refractory to the action of strychnine, or it may be that he employed such powerful 
stimuli that all apparent differences were lost. Sautesson found that strychnine acts twelve times 
more powerfully upon the nerves of Rana esculenta than upon those of R. temporaria. S. Leduc 
believes that he has demonstrated that strychnine can be elect rolytically carried into a human 
nerve and temporarily suspend its functional power (C. R. S. B., 1902, liv.). 



i:\nro-MOTORS 



L35 



Circulation. — The full dose of strychnine produces a rise of the 
arterial pressure which is enormously increased during the convulsion, 
after which there is a very pronounced fall in the arterial pressure.* 
The primary rise is not due to the convulsion, since it precedes the 
convulsion, and occurs in curarized animals. It is largely due to 
vaso-motor contraction, since Mayer, Klapp, and Reichert have all 
found that after paralysis of the dominant vaso-motor centres by 




Fig. 9. — Showing the Effect of Strychnine on the Circulation before and during the 

Convulsive Period. 

The strychnine was injected at the point marked with an arrow ; at C a convulsion occurred. 
Time marker indicates 2 seconds. 

section of the cord, strychnine causes no rise at all,f or an exceedingly 
slight one, of the arterial pressure. The fall of the arterial pressure 
has been shown by Klapp and Reichert to be due, in part at least, 
to paralysis of the vaso-motor centres. By the intravenous use of 
very large doses of strychnine it is possible to produce immediate 
paralysis of those centres, with corresponding fall of the arterial 
pressure. 



* See also Richter (Zeitschri/l f. ration. Med., 1863, xviii.), Denys (Arch. j. Exper. Path. Pharm., 
xx. 306), Kionka (Arch, de Pharmacud. internal., 1898, v.). 

t Schlesinger (loc. tit.) found after the division of the cord that the rise of arterial pressure 
caused by strychnine both absolutely and relatively exceeds that produced in the normal animal. 
This result we believe to have been due to imperfect section of the cord. For an elaboration of the 
reasons for this belief, see tenth edition of this treatise. 



136 GENERAL REMEDIES 

Our knowledge of the cardiac action of strychnine is still imperfect. 
Although Lahousse believes that in any dose strychnine depresses the 
intra-cardiac ganglia, it is probable that the small dose has a stimulat- 
ing influence upon the heart. Igersheimer found that it slowed the 
rate but increased the volume of the wave in the isolated heart of 
either the frog or rabbit, but Kakowski, while he noted the slowing, 
failed to obtain any evidence of increased power. 

In regard to the action of the alkaloid upon the vagi there is much 
difference of statement by investigators. Carl Heinemann, Mayer and 
Klapp all affirm that the heart under the influence of strychnine can 
be arrested by galvanization of the par vagum, but Martin-Magron 
and Buisson, E. T. Reichert and Lahousse, state that the sufficient 
dose of strychnine paralyzes inhibition.* Reichert has found that 
the early effect of strychnine is to stimulate the peripheral inhibitory 
apparatus of the heart, but that if the dose has been sufficient this 
stimulation is followed by pronounced depression or even complete 
paralysis, f 

Blood. — Harley found that blood shaken for twenty-four hours 
with air contained 11.33 parts of oxygen and 5.96 parts of carbonic 
acid; while blood treated in a precisely similar manner, except in 
the addition of strychnine, yielded 17.80 parts of oxygen and 2.73 
parts of carbonic acid. Kionka found that blood taken from the 
strychnized animal does not absorb oxygen with the avidity of normal 
blood, although no spectroscopic changes could be discovered in it. 
Moreover, his analysis of blood gases shows during the dyspnceic 
stage of the poisoning an extreme lack of oxygen without any excess 
of carbonic acid. Maurel states that five centigrammes of strychnine 
sulphate are sufficient immediately to kill the leucocytes in one hun- 
dred grammes of blood, and that in poisoning by strychnine sulphate 
the leucocytes and the animals die at the same time. 

Respiration. — The injection of strychnine produced in the dog an 
extraordinary increase in the respiratory air-movement, which in 
H. C. Wood's experiments never amounted to less than seventy-five 
per cent., and sometimes rose to three hundred per cent. On chloral- 
ized dogs the respiratory effects of the alkaloid were even more 
pronounced. 

Strychnine is among the most certain of the respiratory stimulants, 
its action upon the respiratory centres being evidently a portion of 
its wider influence upon the whole motor tract. 

Temperature. — We know of no recorded temperature-curve in 
human poisoning, but in the lower animals there is usually a primary 
elevation of the temperature followed by a pronounced fall, both 
the rise and fall apparently being in greater or less measure independent 
of the convulsions. 

* For the paper of Brunton and Cash showing that strychnine increases the "refractory period " 
of the isolated frog's heart, see Proc. Roy. Soc, 1883. A consideration of this memoir would require 
an elaborate discussion of the minute points of cardiac physiology, and, as it would throw at present- 
no light upon the practical use of the drug, is not entered upon. 

t Reichert determined that five milligrammes of strychnine per kilogramme of weight will 
paralyze the peripheral vagi in the dog. 



KXC1T0-M0T0RS 137 

According to the experiments of Kionka, during both temperature periods, 
heat -product ion, and heat-dissipation are above the normal, but during the rise of 
temperature the increase in heat -product ion is greater than the increase of heat- 
dissipation, while during t he period of falling temperature the overplus of heat- 
dissipation is greater than that of heat-production. Harnack confirms the results 
of Kionka, but has found also that irregularly at any time during the poisoning there 
may be a sudden arrest of heat -product ion without corresponding fall in heat- 
dissipation, so that the temperature of the animal rapidly descends. Anton 
Obermeier has found that in the rabbit strychnine causes a notable increase in the 
production of carbonic acid, — i.e., of oxidation; and U. Mosso* affirms that even in 
the curarized dog a very pronounced rise of rectal temperature may be produced 
by strychnine. The final fall of temperature is due to the excessive dissipation of 
heat, which in turn is probably the outcome of vaso-motor paralysis. 

It would appear that the action of strychnine upon heat-production 
and heat-dissipation is independent of its convulsive influence, and 
is probably the outcome of some effect upon the central nerve-system, 
but we have not sufficient evidence to determinate the exact nature of 
this influence. 

Eye. — The effect of strychnine upon the normal eye has been 
studied by Von Hippel and Cohn, with rather different results. They 
both, however, found the sharpness of vision increased. 

SUMMARY.— Strychnine has no effect on the cerebrum but is 
a powerful stimulant to the spinal cord. Toxic doses produce vio- 
lent reflex tetanic convulsions, without loss of consciousness, by 
causing such excessive irritability and excitement of the ganglionic 
spinal cells that these cells respond overwhelmingly to the slight- 
est stimuli; they also lower the functional activity of the motor 
nerve-trunks by producing exhaustion and by a direct paralytic 
influence. It increases the blood-pressure by stimulating the vaso- 
motor centre and perhaps also by an action directly on the heart. 
There is also reason for believing that the toxic dose paralyzes 
the peripheral pneumogastric nerve and greatly depresses the heart 
itself and the vaso-motor system. The ozonizing power of the red 
blood-corpuscles appears to be lessened by toxic doses of strych- 
nine. The absorption and the elimination of strychnine are rapid, 
the alkaloid escaping partly in the form of strychnic acid and partly 
unchanged. 

Therapeutics. — Clinical experience shows that strychnine is a 
powerful bitter, tonic, and stomachic, stimulating digestion and 
increasing the appetite, a conclusion which has been elaborately 
confirmed by S. F. Hamper, who, using Ewald's test-breakfast, 
found that the drug increases the volume and digestive power of the 
gastric juice as well as the movements of the stomach. Strychnine 
is, however, more than a mere stomachic: it is a most useful tonic 
when there are general relaxation and loss of nerve-power. A portion 
of its value probably arises from its action upon the spinal motor 

* Denied, however, by M. C. Delezenne, who states that in curarized animals the exhibition 
of strychnine is always followed by an abatement of the central temperature, which is often but not 
aiways accompanied by an increase in the temperature of the surface, which increase he explains 
by the supposition that the drug has the power of dilating the peripheral vessels. 



L38 GENERAL REMEDIES 

nerve-centres; but in all likelihood it influences other portions of 
the cord, affecting the vaso-motor centres, and most probably also 
the trophic centres. Be these things as they may, strychnine is the 
best of all tonics in general functional atony and relaxation. 

Many years ago Trousseau taught that in certain cases of chorea 
minor the strychnine preparations are very valuable, and Morris 
Benedict asserts that the remedy is useful against choreic movements. 
It is not probable that in such cases strychnine exerts any specific 
influence. H. C. Wood has experimentally proved that in choreic 
dogs it greatly increases the activity of the movements; and any 
good which it may achieve in chorea minor is probably due to its 
tonic powers. 

The great influence of strychnine upon the function of voluntary 
motion early led to its use in cases of paralysis, often with the result 
of doing harm rather than good. It is very evident that it can be 
useful only when the paralysis is dependent upon, or at least accom- 
panied by, a depressed state of the spinal motor centres. Whenever 
there is inflammation or irritation of these latter, strychnine may 
do great injury by increasing such irritation, and must never be 
employed. Like galvanism, in hemiplegia it can do only a very limited 
amount of good, and should not be exhibited until irritation from the 
clot has ceased. It is probably useful in many forms of lead paralysis, 
but when the symptoms resemble those of poliomyelitis — i.e., when 
there is a multiple paralysis with rapid wasting of the affected muscles 
and alterations of the electro-contractility — we have found strychnine 
pushed to the verge of poisoning extraordinarily efficacious. 

The value of strychnine in amaurosis was first asserted by Nagel. 
In atrophy of the essential nerve-structure experience has shown, 
however, that little is to be expected from it or any other remedy. 
To be of use the drug must, therefore, be used before the stage of 
atrophy has been reached. It is most useful when employed in 
cases of subsiding neuritis, when atrophy is imminent, as indicated 
by the increasing impairment of vision and the contraction of the 
fields for form and color. Its value in the toxic amblyopias is undis- 
puted, especially where the toxic agent is tobacco or alcohol. The 
distressing headache so frequently present during the progressing 
atrophy of the optic nerves is often signally relieved by steadily 
increasing doses of strychnine or nux vomica, even although the 
advancing loss of vision is not arrested. The prompt action of the 
drug, secured by daily or twice-daily hypodermic injections in the 
temple, seems to offer better results than other methods of adminis- 
tration. The physiologic impression should be maintained by steadily 
ascending doses. Commencing with one-thirtieth of a grain, the dose 
can, within a few weeks, be increased to one-tenth or more, the 
dosage being controlled only by the tolerance of the patient, which 
varies greatly, a slight dryness or sense of constriction in the throat 
or twitching of the calves following the injection being the indications 
as to dosage. The acuity of vision and a widening of the fields may 



K.\ CI TO- MOTORS 139 

often be noted within an hour after the injection, which, however, 

subside to former conditions as the influence of the drug disappears. 
It must be said, however, that in most cases of serious optic neuritis 
t he stage of atrophy is reached and progresses in spite of all known 
medical measures, but in some cases strychnine seems to maintain 
the nutrition of the parts involved until the stage of shrinking is at an 
end, and thus aids in preserving permanently some increment of vision. 

Strychnine in ascending doses is often of signal benefit in restoring 
the proper binocular balance in cases of insufficiency of the ocular 
muscles in debilitated patients, — e.g., after attacks of influenza. The 
strychnine should be given hypodermically in full and ascending 
doses sufficient to produce and maintain a distinct physiological effect. 

As a respirator}' stimulant strychnine is one of our most service- 
able remedies in poisoning by respiratory depressants, in 'pneumonia, 
in suffocative bronchitis, or whenever the respiratory function is 
failing. In long-standing bronchitis or winter cough, and in other 
obstinate pulmonic diseases with dilated right heart, the combination 
of strychnine and digitalis yields most excellent results. Much 
advantage may often be derived, especially in feeble subjects, by 
adding strychnine to the cough mixture. 

The value of strychnine in the treatment of the respiratory acci- 
dents of anesthesia, which was first pointed out in the address of 
H. C. Wood before the Berlin Congress in 1890, is now universally 
acknowledged. Very frequently the best results are obtainable by 
using it in combination with other respiratory stimulants. 

In dyspepsia or constipation or diarrhoea, connected with atony of 
the visceral muscular coat, strychnine is a very valuable remedy. 
In various local paralyses, such as prolapse of the rectum, atonic reten- 
tion of urine, atonic incontinence, and loss of voluntary motion in certain 
groups of muscles from pressure upon or temporary injury of the 
supplying nerve, it may be very useful. There is reason to believe 
that it sometimes does good in these cases by influencing the nutrition 
of the affected muscle or the peripheral nerves; it should be injected 
into the affected part. 

Strychnine is also a serviceable remedy as a stimulant in cases of 
mental and physical depression due to prolonged excitement and 
overwork. J. H. Musser asserts that during the strain of student- 
life before examinations it is especially valuable in preventing the 
development of asthenopia. 

Strychnine is an extremely serviceable remedy in the' treatment of 
cardiac diseases with weakness of muscle. In mitral insufficiency we 
have seen it prolong life for years after the failure of digitalis, and 
when before its administration immediate death seemed inevitable. 
It should always be tried in cases of failing heart where digitalis 
disagrees, it not being possible at present to pick out those cases in 
which brilliant results are to be achieved by it. To be effective it 
must be given in rapidly ascending doses, the patient being kept, 
if necessary, for weeks and months on the verge of strychnine-poison- 



140 GENERAL REMEDIES 

ing, with distinctly heightened reflexes and some muscular stiffness. 
Clinical experience shows that it has no cumulative action, but that 
the patient becomes accustomed to its use, so that a grain a day 
may finally be given without any serious effects. In acute narcotic 
-poisoning, in serious respiratory diseases, in chronic alcoholism, and in 
plumbic poliomyelitis, whenever strychnine is used for a very decided 
immediate effect much larger doses should be employed than have 
been heretofore used. These doses should be given hypodermically 
at intervals of from four to six hours, under the immediate care of a 
trained nurse or other equally skilful person, who should vary the 
dose according to the effect produced. In chronic neurasthenia 
excellent results are sometimes obtained by slowly ascending doses 
carried over a period of one or two years. 

Administration. — As a tonic, strychnine sulphate may be given in 
granule. Whenever it is desired to push the remedy to its physiologi- 
cal limit, it should be given hypodermically in ascending doses until 
restlessness, general excitement, muscular twitching, stiffness of the 
neck or legs, or other symptoms are manifested. In many cases of 
palsies, especially with trophic changes in the muscles, the best effect 
seems to be obtained by injecting the strychnine salt directly into the 
affected muscle. If proper antiseptic precaution be taken, hypodermic 
injections do not cause local irritation. 

Toxicology. — Sufficient has already been said in regard to the 
general symptoms of strychnine-poisoning. It only remains to discuss 
the diagnosis. The symptoms of strychnine-poisoning usually come 
on with great abruptness, within from fifteen to twenty minutes, 
rarely an hour after the ingestion of the drug. Sometimes the con- 
vulsions are preceded by partial spasms of the muscles of the extremi- 
ties, but more often the patient is suddenly thrown down by a general 
tetanic spasm. In this the body is bent backward and rests upon the 
heels and the head, in a condition of opisthotonos; the legs are 
rigidly extended and the feet everted; the arms bent and the hands 
clinched; the eyes staring, wide open; the corners of the mouth often 
drawn up so as to produce the risus sardonicus. The senses may be 
sharpened, but ringing in the ears and dimness of vision may be 
induced if the fits are severe. The face is at first pale, but, if the fit 
be sufficiently severe and protracted, it becomes livid from the inter- 
ference with respiration. Consciousness is not affected, unless when 
asphyxia becomes so pronounced as to threaten death; in such cases 
sometimes a period of insensibility precedes dissolution, but generally 
the intellect is clear to the moment of death. The muscles of the 
jaw are usually the last in the body to be affected, but trismus finally 
comes on in severe cases. The spasms are generally, but not always, 
very painful. There are often erections of the penis, and the feces 
and urine may be passed involuntarily. If the case terminates favor- 
ably, the convulsions gradually lessen in intensity, and fade away, 
leaving the patient exhausted, with a sore, tired feeling in the muscles. 
After death, post-mortem rigidity is developed very quickly. Autop- 



EXCITO-MOTORS 141 

sies have revealed nothing but the usual congestive lesions of death 
from asphyxia, and, at times, indications of spinal hyperemia.* 

Honigmann reports a remarkable case, in which acute inflamma- 
tion of the kidneys followed strychnine-poisoning. 

The minimum fatal dose of strychnine is probably something under 
half a grain; the latter quantity has several times caused death, once 
in a man in twenty minutes; one-third of a grain given at intervals 
in fractional doses has produced such alarming symptoms as to indicate 
that in a single dose it might readily destroy life; one-hundredth of 
a grain is said to have killed a child three and a half months old; 
but ten grains (Tschepke), twenty grains (A. E. Connor), also twenty- 
two grains (George Gray) — taken on a full stomach and retained two 
hours — have failed to cause death, in each case probably on account 
of slow absorption. f 

The question as to the possibility of acquiring immunity to strych- 
nine has become an important one in certain cases of alleged murder, 
and also has some bearing upon the practical use of the drug. Clinical 
experience undoubtedly favors the view that strychnine may be given 
continuously for months or years without any distinct immunity, 
and H. A. Hare has been unable to produce in rabbits by ascending 
doses any distinct lessening of susceptibility to the poison. 

Death from strychnine in man and other mammals mostty occurs 
in a convulsion, and under these circumstances is undoubtedly due 
to asphyxia, caused by the unyielding, spasmodically contracted 
muscles. In man, death sometimes occurs not in a paroxysm, but 
during relaxation, and probably then is the result not only of the 
exhaustion following effort, but also of the direct action of the poison 
upon the respiratory centre and nerves. 

The diagnosis of strychnine-poisoning should usually be compara- 
tively easy. The rigidity during the convulsion and the exaggerated 
reflexes between the convulsions separate it from nearly all forms of 
cerebral spasms. The only conditions with which it is likely to be 
confused are tetanus and certain forms of hysterical convulsions. 
The latter may be distinguished usually by the irregular character of 
the spasm and the presence of hysterical stigmata. From tetanus, 
strychnine-poisoning can be usually easily diagnosed by the sudden 
onset of the poisoning, by the late involvement of the jaw muscles 
and the absence of rigidity between the convulsions, as well as by the 
more rapid course. 

Cases of strychnine-poisoning have, however, occurred in which the symptoms 
have appeared to point towards some cerebral disease or cerebral poisoning. Thus, 
in the case reported by Henry Pilkington, the patient was found unconscious, sur- 
rounded by vomited matters, with excessively uneven pupils and an elevated tem- 
perature. After death both lateral ventricles were found to contain clots, and there 
can be little doubt that the high arterial pressure during an early convulsion had 
produced an apoplexy which was the cause of the subsequent symptoms and death. 

* A lesion found in one case by Moriz Rosenthal may possibly be characteristic. It consists 
of numerous small cross-rents in the heart-muscle, accompanied by small extravasations (Nerven- 
krankheiten, 1870, 334). 

t For small fatal doses see P. J. and TV., viii. 1010, and Guy H. R., 1865, xi. 208. 



142 GENERAL REMEDIES 

It has been asserted that in fatal cases the duration of the attack will always 
distinguish between natural tetanus and that produced by poison. Louis Starr, 
however, reports traumatic tetanus fatal in twelve hours after the first muscular 
t wit rhings, and within one hour and a half after the first convulsion; and death from 
tetanus has occurred fifteen minutes after the reception of the injury (Jaccoud). 

Jn the treatment of strychnine-poisoning no attempt should be 
made to empty the stomach unless the convulsions are under control. 
The passage of the stomach tube may provide sufficient irritation to 
start a fatal convulsion, and it is probable that the irritant action of 
the emetics upon the mucous membrane of the stomach is likely 
also to prove harmful. As a chemical antidote probably the most 
useful substances are either compound solution of iodine or potassium 
permanganate. In the absence of these tannic acid may be adminis- 
tered. For the immediate relief of the spasms some rapidly acting 
depressant is required, such as amyl nitrite or chloroform. If the 
patient is breathing one or the other of these remedies should be given 
by inhalation; when the spasm is so violent as to entirely check the 
respiratory movements, amyl nitrite may be given hypodermically. 
After these substances have been administered, the most useful drugs 
are hydrated chloral and potassium bromide; one-half ounce of the 
bromide with one-half to one drachm of hydrated chloral may be given 
at once, and if necessary one-fourth of these quantities repeated every 
twenty minutes. It is essential to remember that any disturbance of 
the patient may, when the symptoms are well developed, bring about 
a fatal convulsion; thus, we have seen death occur in a convulsion 
caused by the effort to get the mouth open to give the remedy. If 
the patient is unable to swallow, the chloral or bromide may be given 
by rectal injection. Artificial respiration, which has been highly 
commended by some, cannot, we believe, ever be of service in human 
poisoning. 

Leube was, we believe, the first to demonstrate that forced artificial respira- 
tion in animals will not only very greatly lessen the production of convulsions by 
strychnine, but will also affect the final result of the poisoning. After considerable 
discussion, the accuracy of the results reached by Leube has been finally estab- 
lished. The method in which the forced respiration acts is at present unknown. 
It has been shown by W. J. Gies and S. J. Meltzer that while artificial respiration 
completely suppresses the reflex irritability due to strychnine-poisoning, it does not 
distinctly affect the increased reflex irritability induced by section of the spinal 
cord: that the influence of the artificial respiration is not the result of any super- 
oxidation of the blood seems to be proven by the fact discovered by Gies and 
Meltzer, that insufflation of the lungs of the animal with pure hydrogen gas has 
the same effect as artificial respiration. None of the ordinary methods of artifi- 
cial respiration in man is sufficiently powerful to be of any value, while the 
manipulations of the physician would certainly tend to increase the strychnic 
spasm. The curious discovery of Leube is therefore of scientific rather than of 
practical value.* 

* Gies and Meltzer found that the animal under strychnine could be kept alive by insufflation 
of pure hydrogen for thirty minutes, without manifesting any signs of asphyxia, dyspnoea, or 
cyanosis. This is so absolutely destructive of the foundations of modern physiology that it is 
impossible to avoid believing there was some mistake or fallacy in the experimental technic. The 
literature of this subject is so thoroughly given in the paper of Gies and Meltzer that we content 
ourselves with adding Jochelsohn {Rossbach's Untersuchungen, i. 92). 



BXCITO-MOTORS 143 

Brucine. — Strychnine clings so closely to brucinc that the physio- 
logical actions attributed to brucine may be in truth caused by con- 
taminating strychnine. L. Wintzenreid found that brucine acts as 
a stimulant to the spinal cord and a paralyzant to the motor nerves, 
but does not influence the cerebrum or the sensory nerves; and that 
in the higher animals, at first it increases the arterial pressure and 
afterwards lessens it, in large doses paralyzes the vagi, causes death 
by asphyxia, and in other ways acts like strychnine. The more recent 
experiments of Lauder Brunton are in accord with the results obtained 
by Wintzenreid in showing that brucine causes spinal convulsions in 
mammals when injected directly into the circulation. Brunton found, 
however, that when taken by the mouth it produces no symptoms, 
probably because it is excreted as rapidly as it is absorbed. In an 
elaborate study, Edward T. Reichert reached the conclusion that the 
physiological action of brucine is precisely that of strychnine, except 
that brucine is much less rapidly absorbed, is from forty to fifty times 
less powerful as a convulsant, is more poisonous to the sensory nerves, 
and is more uncertain in its effect upon bodily temperature. Further, 
brucine appears to have an action upon the volitional centres of the 
frog different from that of strychnine, producing a brief period of 
motor paralysis preceding the stage of spinal convulsion (Mays, 
Reichert).* Thomas I. Mays found that brucine locally applied to 
the nerves of the frog rapidly produces a paralysis of the sensory 
fibres. This led him to test it as a local anesthetic in man, and he 
asserts that a five- or ten-per-cent. solution applied to the mucous 
membrane of the mouth caused rapid loss of sensibility; also that a 
twenty-per-eent. solution applied to the back of the hand caused 
pronounced impairment of sensibility. Mays used this solution with 
excellent results for the relief of the itching of chronic 'pruritus. Ralph 
W. Seiss and Charles H. Burnett have found that the application of 
a five-per-cent. solution in the local pruritus of inflammation in or 
about the external ear usually gives very marked relief. Burnett 
states that his results were far more satisfactory than those which 
he has obtained with cocaine. In using brucine as a local anesthetic 
it is essential that it be chemically pure: the nitrate or the sulphate 
may be selected, and one minim of hydrochloric or sulphuric acid 
should be added to the solution for each three grains of the alkaloid 
salt. 

REFERENCES. 

STRYCHNINE. Cohn W. M. W., 1873, No. 42. 

T> Xlf At m , m , r Connor O. M. R., 1879, 12. 

Benedict W . M. W ., 1891, xli Delezenne Bull. M<5d. du Nord, 1895, 

Bernard Lecons sur les substances 



XXXI V. 



Biernacki Th. M., xii. 



Toxiques. Demme Sy'd. Soc. Yearbook, 1865 



60, 441. 



Borzi A. I. B., 1899. Derby B. M. and S. J., 1902, cxlvi, 

Bouley and Colin. .Traite' de Physiol.com- 508. 

paree, ii. 91. Falck Cb. M. W., 1899, xx. 

Carrara Cb. Inner. Med., 1901. Gies and Meltzer. .J. Ex. M., 1902, vi. 107. 



* For a research showing the comparative action of strychnine and brucine on different species 
of frogs, see Sautesson (Archiv /. Exper. Path. u. Pharm., xxxv.). 



144 



GENERAL REMEDIES 



REFERENCES (Continued). 



Gray 

Hamper. . . . 

Hake 

Hareey. . . . 
Harnack. . 
honigmann 

IgERSHEIMKK 

Jaccoud. . 
Kakowski 

KlONKA. . . 

Klapp. . . . 

Kollikek. 
Krattkh. . 
Lahodsse. 
Lesser. . . 

Leube 

Lovett. . . 

Maurei 

Mayer 



Meltzer 

Meltzer and 

Mosso 

Musser 



. .B. M. J., 1880, i. 477. 
..L. M. R., Feb. 1891. 
..A. J. P., 1901, v. 
..L. L., July, 1866. 

. .A. E. P. P., 1903, xlix. 

. .S. Jb., ccxxiii. 21. 

..A. E. P. P., cliv. 73. 

. .Path. Intern., i. 441. 

. A. I. P. T., xv. 21. 

. .A. P. I., 1898, v. 111. 

. .J. N. M. D., Oct, 1878. 

. .V. A. P. A., x. 

. . W. M. W., 1882. 

..C. R. S. B., xci. 

. . \ ierteljahrschr. f. gericht, 
Med., 1898, xv.27 and 261. 

. .A. A. P., 1807, 030. 

..J. P., ix. 

. . B. G. T., March, 1892. 

..Med. Jahrb. d. k. k. Gesell- 
schaft d. Aertz zu Wien, 
1872, 112. 

J. Ex. M., i.; A. J. M. S., 

Nov. 1899. 
Lanomann.J. M. R., 1903, ix. 

LI. B., 1886. 

. ...T. G., U. 10. 



Nagel, 



Obermeier. . 

PlLKINGTON. 

Plugge 

PoULSON. .. . 

Rautenfei.d 
Reich ert. . . 
Saltesson. . 

Starr 

Tschepke.. . 
Van Deen . . 



Von Hippel. 



Wood 

Wormley. 



Brdnton 

Igersheimer 
Kakowski. . 

Mays 

Reichert. . . 

Seiss 

Wintzenreid 



. . Die Behandlung der Amau- 
rosen u. Amblyopeen mit 
Strychnin, Tubingen, 1871. 

. .In. Dis., Erlangen, 1891. 

. .L. L., 1893, i. 

. .Arch. d. Pharm., 1883. 

. .A. E. P. P., xxvi. 

. . In. Dis., Dorpat, 1884. 

. .T. G., April, 1892. 

. .A. E. P. P., 1894, xxxv. 

. .P. M. T., iii. 311. 

. .D. K. C., 18G1. 

. .Physiol, de la Moelle e'pi- 
niere, 1860, iii. 130. 

. .Wirkung des Strychnins auf 
die normale und kranke 
Augen, Berlin, 1873. 

. .J. P., 1892. 

. .Micro-Chemistry, 2d Ed. 

BRUCINE. 

. .J. Chem. S., 188. 

. .A. E. P. P., cliv. 73. 

..A. I. P. T., xv. 21. 

. .J. P., viii. 

. .M. News, April, 1893. 

. .T. G., xviii. 459. 

. .In. Dis., Geneva, 1882. 



FAMILY VI.— DEPRESSO-MOTORS. 



Under this heading are considered certain drugs which are used 
for the purpose of lessening the activity of the spinal cord. They 
have, except in this particular, but little in common in their action, 
and must be studied individually. 




Fig. 10. — Diagram to Illustrate the Action of the Depresso-Motors. 

B. — Psycho-motor centre in the brain. M.G. — Motor ganglion in spinal cord. M. — Muscle. 
y. Sensory nerve endings. S.G .—Ganglion on the posterior (sensory) nerve root. 

Paralysis of the motor ganglia or motor nerve abolishes both voluntary and reflex movement; 
paralysis of the sensory system destroys reflex but not voluntary motion because the pathway from 
the brain to the muscle remains intact. 

Phvsostigmine, the Nitrites, Gelsemmine and Chloral Hydrate depress M.G. Ihe Bromides 
depress'S.G. Lobelia, Coniine, and Gelsemine paralyze the motor nerve endings in M. Ether and 
Chloroform depress both M.G. and S.G. 

PHYSOSTIGMA. 

This substance commonly known as Calabar bean is an irregular, 
kidney-shaped bean, about an inch in length and three-fourths of an 
inch wide, the product of the Physostigma venenosum, a perennial 
woody creeper of Calabar, Africa, where the bean has been used by 
the natives as an ordeal test for criminals, witches, etc., since time 
immemorial. It owes its activity to the alkaloid physostigmine, or 
eserine, of which it should contain 0.15 per cent. E. Harnack and L. 
10 145 



146 GENERAL REMEDIES 

Witkowski have described a powerful tetanizing alkaloid, calabarine, 
which is sometimes abundant in commercial extracts of Calabar bean. 
It is probably a decomposition product from that alkaloid (see also 
Husemann). Isophysostigmine according to Ogiu is similar in its 
action to physostigmine but more powerful. 

Official Preparations : 

Extract urn Physostigmatis i to \ grain (0.008-0.015 Gm.). 

Tinctura Physostigmatis (10 per cent.) . .20 to 40 minims (1.2-2.5 C.c). 
Physostigmine Salicylas [Eserine Salicy- 
late] & to jV grain (1-2 Milligm.). 

Physostigminaj Sulphas T ,' - to fa grain (1-2 Milligm.). 

Absorption and Elimination. — No apparent irritant action occurs 
from therapeutic doses of Calabar bean or its alkaloid. 

Both absorption and elimination are very rapid. N. Teich and D. 
Schweder have both found physostigmine in the urine half an hour 
after its ingestion. Although the alkaloid has been detected in various 
secretions by Dragendorff and his pupil Pauder, it chiefly escapes 
through the kidneys. Its effect upon the urinary secretion has never 
been studied, excepting in that Merson states that it decreases the 
excretion of urea and other urinary solids in paresis. 

Physiological Action. — Nervous System. — Physostigmine is a 
depressant to the motor side of the spinal cord. Upon the cerebrum 
it has no perceptible influence. It is feebly depressant to both motor 
and sensory nerves but the paralysis and loss of reflex activity which 
it produces are. undoubtedly due to its action upon the cord. 

When an animal receives a small fatal dose of Calabar bean, after a time mus- 
cular tremors appear, and almost immediately the victim falls to the ground, or 
lies down, in a state of perfect muscular flaccidity. The pupils generally contract, 
and the respirations become slow, irregular, and often stertorous. All reflex actions 
are almost at once diminished, and this diminution grows greater and greater, until 
it ends in their complete abolition. So long as the condition of the motor system 
allows of it, evidences of sensibility are manifested whenever the animal is in any 
way injured. According to dementi Papi, the voice is completely lost. The mus- 
cular tremors persist during the whole period of paralysis, and, indeed, even after 
cessation of the respiration. They vary greatly in intensity, and in some cases are 
so severe (Fraser) as to simulate general convulsions. As the minutes go by, the 
rhythm of the respiration becomes more and more affected, and at last death takes 
place from asphyxia. 

Fraser, Harnack, Witkowski, and others have found that if in the frog a periph- 
eral nerve be protected by tying its artery and the batrachian be poisoned with 
Calabar bean, the paralysis in the protected limb occurs pari passu with that in the 
remainder of the body. Further, Fraser has found that when the poison is applied 
directly to the cord, fibrillary contractions, due probably to a local irritant influence, 
are induced in the muscles supplied from below the point of application, but in a 
little while all movements cease, and even galvanization of the cord itself is unable 
to elicit response. It is asserted by Papi and other investigators that the extremely 
minute dose of physostigmine acts as a stimulant to the spinal cord. Although 
this may be true, it seems at present writing improbable.* 

* Kohler, Rossbach, and others have affirmed that Calabar bean produces a tetanic intoxication. 
A plausible explanation of these singular observations, and of many of the discrepancies of authori- 
ties, is to be found in the discovery of calabarine. Its discoverers state that it produces first a 
violent tetanus, and afterwards paralysis. It is plain how its presence in varying amounts in Calabar 



DEPRESSO-MOTORS 147 

Although there is reason for believing that physostigmine is capable of affecting 
both motor and sensory nerve-trunks, yet this action is so feeble as probably to 
take no part in the production of symptoms. The afferent nerves are less sensitivo 
than the efferent, since Fraser has found, first, that the local application of a strong 
solution of the poison to a nerve kills the efferent or motor fibres before the afferent 
or sensory, although the functions of both of them are finally abolished; second, 
that when the arteries in the left leg of a frog are tied, and the animal poisoned 
both with Calabar bean and strychnine, there comes a time when reflex movements 
are excited in the left leg by irritation of the right foot, although irritation of the 
left foot does not. cause movements in the right leg, — i.e., the impulse is able to 
travel up the poisoned nerve of the right leg but not down it. 

The extreme feebleness of the influence of physostigmine is shown by the fact 
t hat the frog's nerves are often active after death from physostigma (Laschkewich, 
Vintschgau, and Fraser); and Fraser has determined that after the fatal result 
has been produced rapidly with physostigmine, the rate of conduction of impulse 
is as rapid in the nerve to which the poison lias had free access as in one which has 
been protected by the tying of its artery. 

Loss of power in the motor nerves after poisoning by Calabar bean has been 
found only in the frog, and further, only when the dose has been so small that the 
heart has continued to beat long after the cessation of respiration, so that the nerves 
had been, as it were, macerated in a solution of the poison. Harnack and Witkowski 
deny that physostigmine has even this feeble influence upon the nerve-trunks. 
The loss of power is probably in the termination of the nerve rather than in the 
trunk, for Fraser found that when all the blood-vessels supplying the gastrocnemius 
muscle were cut in a frog and the animal poisoned, at a certain time irritation of 
the crural nerve produced spasms of the gastrocnemius alone. 

Muscles. — The large dose of physostigmine produces violent 
muscular tremors. The continuance of these movements after death 
indicates that they are due to a direct action of the drug upon the 
muscles. This conclusion is established by the experiments of Lasch- 
kewich, of Fraser, and of Leven and Laborde. All of these investi- 
gators have noted that after death these contractions are increased 
by exposure to the air and by direct stimulation of the muscles; and 
Fraser has found that they occur in the frog during life after section 
of the supplying nerve, and also in a muscle actually cut out of the 
body. Laschkewich has confirmed the latter fact in the case of warm- 
blooded animals, and Leven and Laborde have proved that previous 
destruction of the lower end of the spinal cord in a guinea-pig does not 
prevent the development of the muscular twitchings in the hind legs. 
Schweder contends that the action of the poison is not, however, 
upon the muscular structure itself, but upon the peripheral nerve- 
endings in the muscle, basing his conclusions especially upon the 
asserted fact, that previous hypodermic injections of atropine or 
curare prevent the development of rigidity in the snake poisoned with 
physostigmine. It is certain that the final paralysis produced by 
physostigma is not of muscular origin, since at the time of death the 
contractility of the muscles is in no way diminished, but, on the 
contrary, Fraser has noted that loss of contractility and rigor mortis 
are greatly delayed in Calabar-bean poisoning. 

bean preparations would modify their action. The researches of Kohler, of Vintschgau, and of 
Rossbach and Frohlich are especially open to doubt, on account of their statements that Calabar 
bean tetanizes. It is very probable that the extracts used by them contained a notable percentage 
of calabarine. 



148 GENERAL REMEDIES 

Circulation. — In the mammal, after therapeutic and even toxic 
doses, the cardiac action of physostigmine is subordinate to its influ- 
ence upon the nerve-centres. In moderate doses, however, it causes 
a marked slowing of the pulse with some rise in the arterial pressure. 
The slowing of the pulse is probably due to a stimulation of the 
intracardiac terminals of the vagi, although some authorities attribute 
it to an action on the heart-muscle. The rise of pressure is brought 
about by an influence on either the heart or arterial muscles. As has 
been shown by Fraser, when overwhelming doses of the poison are 
administered, especially if they be injected into the jugular vein, 
death results from syncope, or from consentaneous failure of the 
cardiac and the respiratory functions, and the heart is found arrested 
in diastole, flaccid, but, according to Fraser and to Arnstein and 
Sustschinsky, responding, though feebly and uncertainly, to direct 
stimulation. In the poisoned frog the early contractions of the heart 
are slower and more forcible than the normal (Harnack and Wit- 
kowski); while the arrested heart is insensible to stimuli (Rossbach 
and Frohlich). 

Although, according to the experiments of Fraser, there is at first a slight fall 
of the blood-pressure, which is probably due, as he believes, to diminished pulse- 
frequency, yet, in spite of the continuance of the slow pulse, the arterial tension 
soon recovers itself, and remains for a long time much above the normal point, 
while at the same time the individual cardiac beats are greatly increased in strength 
(Fraser, Bezold and Gotz*). Finally, the arterial pressure falls far below normal, 
and the power of the heart is gradually extinguished. 

That the rise of arterial pressure must be largely the result of a stimulant action 
upon the heart or upon the vessel-walls is shown by the finding of Bezold and Gotz, 
that the arterial pressure still rises under the influence of physostigmine after sec- 
tion of the spinal cord; and by that of Harnack and Witkowski, that when the 
vaso-motor centres are paralyzed with chloral, physostigmine causes a very decided 
increase of the arterial pressure. The facts — that section of the vagi does not inter- 
fere with the production of the cardiac phenomena of Calabar bean, and that in the 
frog physostigmine acts in its usual way on the heart, although the brain and medulla 
have been destroyed (Vintschgau) ; also that when physostigmine is placed directly 
on the heart, or into one of its chambers, it causes a long diastolic pause, followed 
by contractions, interrupted by pauses, and finally by resumption of regular 
contractions, or else by diastolic arrest, the heart still retaining its power of 
responding in an embarrassed manner to stimuli (Fraser) — would appear to demon- 
strate that physostigmine directly affects the heart. How far this influence is upon 
the cardiac ganglia and how far upon the muscle-fibre has not been determined. 
It seems, however, probable that physostigmine affects the cardiac muscles in the 
same way as it does the muscles of voluntary life. 

There is, however, much reason for believing that physostigmine affects the 
peripheral inhibitory apparatus, although the evidence is not entirely clear. Arn- 
stein and Sustschinsky found in rabbits and also in guinea-pigs that the influence 
of galvanic irritation of the vagi upon the heart is much greater after than before 
poisoning with physostigmine, diastolic arrest being produced much more easily 
and continuing much longer than normal after the withdrawal of the stimuli. More- 
over, after having completely paralyzed the peripheral cardiac vagi in the rabbit 
by large doses of atropine, they restored functional power to these nerves by injec- 
tions of Calabar bean. If the accuracy of these experiments be admitted, it must 

* We have not seen the original paper of these authorities in the Centralblalt fur Med. 
Wisaenschaft, 1807, but quote them from the paper of Arnstein and Sustschinsky. 



DEPRESSO-MOTORS 149 

also be admitted that physostigmine is a powerful stimulant to the peripheral 
cardiac inhibitory apparatus. Kohler, however, using the frog, and Rossbach and 
Frohlieh, using the rabbit, failed to resuscitate the atropinized vagi by means of 
physostigma, but a negative result in such a case might be due to an improper 
proportion in the doses of the counter-poison, or to the atropine being employed 
in overwhelming amount. 

Physostigmine appears to have no paralyzing effect upon the vagi; at least in 
warm-blooded animals these nerves are never paralyzed (Fraser, Arnstein and 
Sustschinsky, Harnack and Witkowski); and the loss of functional power which 
lias been detected by Fraser, Rossbach and Frohlieh, Harnack and Witkowski, in 
the vagi of the frog does not appear until so long after the cessation of respiration 
that it is very probably a secondary result. 

The question as to the effect of physostigmine upon the blood-vessels cannot 
at present be positively answered. Evidence concerning it has been brought for- 
ward by Fraser and Harley in the form of observations made upon the web of the 
frog. We have already stated our belief that tins sort of evidence is of very little 
value. In the present instance, as usual, it is entirely contradictory as given by 
different observers. (For details, see tenth edition of this treatise.) 

The fact that the rise of arterial pressure produced by physostigmine after 
section of the cord is not nearly so great as in an uninjured animal suggests, but 
does not. prove, that the drug affects the vaso-motor centre. Analogy makes it 
probable that the muscular fibres in the coats of the vessels share the wide-spread 
muscular action of the poison, and that the peripheral contraction of the arteries 
is an efficient cause in producing rise of blood-pressure. In considering the general 
physiological action of the drug, it must not be forgotten that its influence upon 
the heart is entirely subservient to its influence on the nervous system,* and that 
death in the mammal occurs before the stage of cardiac palsy is reached unless 
the drug be injected directly into the heart in overwhelming dose. 

Blood. — According to Fraser, after death from physostigmine the 
blood coagulates slowly and loosely, and the red disks present various 
irregularities of outline; it is probable that these changes are due to the 
long asphyxia, and that the poison does not directly affect the blood. 

Intestines. — Intestinal peristalsis is primarily much increased by 
the action of physostigma (Westermann, Papi, Fraser). After poison- 
ous doses there is at first a stage of exceedingly active movements in 
the bowels; then spasmodic tetanic contraction of the intestines 
occurs, so that their calibre is very much diminished; and finally 
relaxation and dilatation take place. After death the vermicular 
movements are found very much lessened (Fraser) or altogether 
abolished (Tachau). The action of the drug upon the intestines appears 
to be peripheral, due to contact of the poison in the blood with the 
muscular fibres or the nerve-elements in the walls of the bowels; 
for Westermann found that extirpation of the cardiac ganglion had 
no effect upon the action of the drug, but that tying of the mesenteric 
and of the cceliac arteries, before poisoning, prevented any increase 
in the peristalsis. 

Secretion. — Physostigmine probably increases nearly all secretions. 
Its action upon the salivary glands is often decided, and, according 
to Heidenhain, is not prevented by atropine. 

* For a discussion of the peculiar cardiac relations of physostigmine and muscarine, see the 
paper by Harnack and Witkowski. Those authors believe that Calabar bean sets in motion the 
heart arrested in diastole, not by paralyzing the cardiac inhibitory apparatus, but by stimulating 
the cardiac muscle. 



150 GENERAL REMEDIES 

Eye. — Physostigmine produces a contraction of the pupil, when 
applied locally, by its effects probably upon the peripheral endings 
of the nerves. In its action there is probably a combined paralysis 
of the peripheral terminals of the sympathetic and stimulation 
of the oculo-motor nerve-endings. Within certain limits it will 
overcome the effect of atropine. 

The closeness of the analogy between the pupillary action of atropine and that 
of physostigmine is seen in the fact that, like the former, the latter, as shown by 
the experiments of Vee and Leven on chickens, does not affect the irides of birds. 
It is probable that the two alkaloids are directly antagonistic in their action upon 
the peripheral nerve-endings in the pupil. 

It has been held by various authorities that if galvanization of the sympathetic 
fibres in the neck fails to expand a contracted pupil, the myosis must be due to 
paralysis of the sympathetic. Evidently, however, this is asserting too much, for, 
as pointed out by Griinhagen, it is conceivable that an oculo-motor spasm can exist 
of such intensity that the antagonistic nerve is unable to dilate the pupil. The 
testimony as to whether galvanic stimulation of the sympathetic does or does not 
dilate the physostigminized pupil is somewhat conflicting. Schultz, and Griin- 
hagen, each affirms that dilatation always occurs; while, on the other hand, Gustav 
Engelhardt has found that galvanization of the cervical sympathetic has no effect 
upon the physostigminized pupil. The experiments of Fraser, of Bernstein and 
Dogiel, and of Rosenthal would seem to reconcile these differences, and, by their 
accord, to prove that under the maximum influence of Calabar bean the sympathetic 
nerve is powerless, while when the contraction is the result of a milder influence of 
the drug, stimulation of the sympathetic nerve will cause some dilatation.* Fraser, 
and also Engelhardt, have found that if the poles of a battery be applied directly 
to an iris even most profoundly contracted by physostigma, immediate dilatation 
occurs. 

On the other hand, the well-known force of the myosis indicates that it is not 
due simply to loss of power in the dilating fibres; an indication which is corroborated 
by the fact that section of the cervical sympathetics will not produce a myosis as 
complete as that caused by physostigmine. 

SUMMARY. — The dominant physiological action of physostigma 
is a persistent depression of the motor centres of the spinal cord, in- 
volving also the respiratory centres in the medulla, and producing loss 
of reflex action -with an increasing paralysis, ending in death from 
centric paralytic asphyxia. Contraction of the pupil is usually seen in 
the poisoning, and is always produced by the local application of the 
drug ; it is due to a peripheral influence and probably to paralysis of 
the sympathetic nerve -filaments with stimulation of the oculo-motor 
nerve-endings. The motor nerve-trunks are scarcely affected, but in 
slow poisoning probably suffer some depression of function which 
especially affects their peripheral endings. Neither the cerebral cortex 
nor the sensory nerve nor the sensory nerve-centres are acted upon, 
unless secondarily in the latest stages of poisoning. Physostigma acts 
as a stimulant directly either upon the muscle structure itself or upon 
the peripheral nerve-endings in the muscles. The influence of the drug 
upon the circulation is entirely subordinate. Early in the poisoning 
there is a rise of the blood-pressure, which is in great part, if not alto- 

* More recently Rossbach and Frohlich affirmed that galvanisation of the sympathetic still 
causes dilatation, even when the action of the physostigmine is most vigorous. As it is scarcely 
conceivable that the various other investigators should have been so much in error, it is probable 
that Rossbach and Frohlich used such strong currents that thev were directly transmitted to the iris. 



DEPRESSO-MOTORS 151 

gether, due to a direct stimulation of the cardiac muscle or its con- 
tained ganglia, although it is probable (not proved) that there is some 
contraction of the blood-vessels, which may be due to an influence 
upon the muscle-fibre in the vessel-walls similar to that upon other 
muscle-fibres, striated and non-striated. We have no information as 
to the effect of the poison on the vaso-motor centre. According to 
some authorities, the peripheral vagi are strongly stimulated. Intes- 
tinal peristalsis is greatly increased by the direct action of physostigma 
upon the muscular fibres or the peripheral nerve-endings in the intesti- 
nal -walls. The alkaloids of Calabar bean are rapidly absorbed, and 
are eliminated chiefly by the kidneys. 

Therapeutics. — The action of physostigma upon the spinal cord 
very early led to its use in spasmodic affections, and especially in 
tetanus. In the paper of B. Roemer are collected forty-seven cases, 
of which twenty proved fatal.* In trismus neonatorum, it has been 
employed with results certainly no more encouraging than those 
obtained in tetanus. In chorea it has also been used by some prac- 
titioners with asserted advantage, but further experience hardly 
justifies its administration. 

The physiological action of physostigmine upon the unstriped 
intestinal muscle-fibres has led to its employment in atony of the mus- 
cular coat of the bowels and other similar organs. V. Subbotin has 
used the extract with the happiest results in a case of chronic bronchial 
catarrh with intense dyspnwa, believed to be due to weakness of the 
bronchial muscular fibres, and also in one of apparently "phantom 
tumor," with chronic intestinal dyspepsia and catarrh. In constipation 
dependent upon relaxation, and as an addition to laxative pills, we 
have found it very useful. A. Hiller strongly endorses the value of 
the extract in chronic intestinal atony, after or during a catarrh, in 
the convalescence from fever, etc., and in constipation with flatulence, 
in meteorism, etc. 

Calabar bean has also been employed in strychnine-poisoning , and 
a recovery obtained after the ingestion of three grains of the latter 
alkaloid is reported by J. W. Keyworth. 

In epilepsy, some trials have been made of the drug, but its value 
is very doubtful. Harnack and Witkowski have found that in epileptic 
guinea-pigs physostigmine causes a succession of fits lasting for hours 
and days. They have further noted a similar influence upon man. 
Attention has also been called to the employment of physostigma as 
a galactagogue, the extract being applied to the breast itself. 

Ophthalmic Uses.'f — The instillation of a drop of a one-quarter to 
one-half-per-cent. solution of eserine sulphate into the eye is followed 
by strong contraction of the sphincter of the iris and by spasm of the 
ciliary muscle which adapts the eye for the near point. Its action 
begins in about one minute, usually reaching its maximum in from 
twenty to thirty minutes, and lasts from twenty-four to thirty-six 

* For references to additional cases see 13th edition of this work. 

t This section has been written by Professor George E. de Schweinitz. 



152 GENERAL REMEDIES 

hours. The intra-ocular tension is reduced, provided it has been 
raised above the normal point before the application of the drug. 
Eserine, when first instilled into the eye, is apt to produce twitching 
of the eyelids and sharp supra-orbital pain due to its causing spasm of 
accommodation. It is used by ophthalmologists: First, to reduce 
abnormally high intra-ocular tension, particularly in glaucoma, and 
in those ocular conditions in which, other things being equal, it is 
desired to diminish the intra-ocular tension; second, to prevent pro- 
lapse of the iris after simple cataract extraction, and sometimes to 
reduce a prolapse when this has occurred in the periphery of the 
cornea as the result of an operation or of a perforating corneal ulcer; 
third, to limit the progress of deep ulcers near the margin of the cornea, 
because it is supposed to promote absorption through dilatation of 
the ciliary vessels and to check the sloughing process; fourth, to 
counteract the effect of the milder acting mydriatics, — for example, 
homatropine, — especially in eyes in which their use has tended to 
raise intra-ocular tension; fifth, to overcome paresis of the ciliary 
muscle resulting from various diseases, — for example, diphtheria, 
diabetes, syphilis; sixth, to reduce the vascularization in certain 
types of keratitis, episcleritis, and scleritis, provided there be no asso- 
ciated iritis. Eserine too freely used, especially in hyperemic eyes, 
is capable of causing slight iritis, the so-called eserine iritis. If the 
indications for a local anesthetic are present in conjunction with those 
demanding a myotic, there is no objection to combining in the same 
solution eserine and cocaine, or eserine and dionine. 

Administration. — Physostigma is frequently administered as an 
extract, but the alkaloid is preferable, on account of its certainty. 
The salicylate is preferable to the sulphate as more permanent, the 
sulphate being very deliquescent. 

Toxicology. — So far as we know, Calabar bean has not been used, 
either in Europe or in this country, with criminal intent. In Liver- 
pool seventy children were accidentally poisoned at one time.* Many 
of the victims vomited spontaneously, and thus relieved themselves. 
Those brought to the hospital were in a state of extreme prostration 
and muscular relaxation. They appeared to suffer almost no pain, 
some of them, however, saying that they had a "belly-ache." Among 
some thirteen examined, one had the pupils contracted. The only 
child who did not recover was excessively weak, and, crying out 
suddenly, was dead of syncope. The heart was found relaxed and 
flabby, both sides equally full of blood. Half a bean produced in a 
strong manf great muscular weakness, tightness across the chest, 
temperature of 96.6° F., very slow, intermittent, irregular pulse, and 
collapse, without vomiting, purging, contraction of the pupils, or 
abdominal pain. Lodderstaedt reports a hypodermic injection of one- 
half a milligramme of the physostigmine sulphate in a boy nine years 
old, followed in a quarter of an hour by violent headache, free sweat- 

* See M. T. G., Oct. 1864, 406. 

t See St. Bartholomew Hosp. Rep., 1879, xv. 



DEPRESSO-MOTORS 153 

ing, salivation, slowing of the pulse, repeated vomiting, contraction 
of the pupils, and, finally, deep collapse, from which, however, the 
patient recovered. Two girls took between them 0.1 gramme (1.53 
grains) of physostigmine, with the result of sudden unconsciousness, 
great redness of the face, muscular relaxation, vomiting, widely 
dilated, immovable pupils, and, on recovery of consciousness, violent 
abdominal pains, with pulse 60, and hard; recovery after some 
hours (Leibholz). 

In 1SG4 Kleinwachter first used successfully atropine in physo- 
stigma-poisoning, and thereby started much discussion and research. 

Bourneville detailed in 1867 some experiments which seemed to show that 
there is a real antagonism between Calabar bean and the mydriatic, and in 1870 
published five experiments upon guinea-pigs, which were very decisive in that a 
proved fatal dose of physostigmine was given in each case and recovery obtained 
by the use of non-lethal doses of atropine. In 1869 Roberts Bartholow, of 
Cincinnati, on the strength of a few really indecisive experiments, arrived at a 
conclusion opposite to that of Bourneville. 

In an extremely thorough research, which might well serve as a model to any 
one studying the antagonistic action of poisons, Fraser demonstrated that within 
certain limits atropine may be relied upon as a counter-irritant poison to physo- 
stigmine. He found that in the rabbit one-fiftieth of a grain of atropine could success- 
fully antagonize one and a half but not twice the minimum fatal dose of Calabar 
bean, one-fortieth of a grain of atropine could overcome two to two and a half times 
the minimum lethal dose of physostigmine, and three-fiftieths was sufficient for 
three times the minimum fatal dose. When four times the lethal dose of physo- 
stigmine was given to the rabbit, atropine was powerless to do good. In all these 
cases the atropine was given five minutes after the physostigmine. No experiments 
were made by Fraser to test the value of physostigmine in atropine-poisoning. 
These experiments of Fraser have been in some degree confirmed by the imperfect 
researches of Amagat. 

J. Pal asserts that physostigmine is an antidote to curare; it 
being possible with it to bring about voluntary respiration in an 
animal which has been entirely paralyzed by the South American 
poison. We know of no experiments as to the value of curare in 
physostigmine-poisoning. 

HYDROBROMIC ACID. 

Hydrobromic acid is recognized by the Pharmacopoeia in the form 
of a ten-per-cent. solution. This is a colorless, odorless liquid with a 
strongly acid taste. On account of its irritant action upon the stomach 
it is comparatively little used in the form of the acid itself but is chiefly 
employed in the form of one of its salts. Of these there are official, 
ammonium, calcium, lithium, potassium, sodium and strontium 
bromides.* These all occur in the form of colorless or white crystals 
of a bitterish salty taste, freely soluble in water and, with the excep- 
tion of potassium bromide, also soluble in alcohol. All except the 
potassium and ammonium salts are more or less hygroscopic. 

* Zinc bromide is also official but has no useful place in therapeutics. 



[54 GENERAL REMEDIES 

Incompatibilities. — The hydrobromides of many of the alkaloids 
are insoluble in water and therefore care should be observed in com- 
bining bromides in solutions containing alkaloids. Potassium chlorate 
and tincture of ferric chloride liberate free bromine when brought 
into contact with the salts of hydrobromic acid. The bromides are 
also incompatible with spirit of nitrous ether and with calomel. 

Official Preparations : 

Acidum Hydrobromicum Dilutum (10 per 

cent.) 1 fluidrachm (4 C.c.). 

Ammonii Bromidum 10 to 60 grains (0.6-4.0 Gm.). 

Calcii Bromidum 10 to 60 grains (0.6-4.0 Gm.). 

Lithii Bromidum 10 to 60 grains (0.6-4.0 Gm.). 

Potassii Bromidum 10 to 60 grains (0.6-4.0 Gm.). 

Sodii Bromidum 10 to 60 grains (0.6-4.0 Gm.). 

Strontii Bromidum 10 to 60 grains (0.6-4.0 Gm.). 

Absorption and Elimination. — The bromides are freely absorbed 
and circulate in the blood as a bromide. Elimination takes place to 
a certain extent through the skin, and probably largely through the 
intestinal mucous membranes, though the chief avenue is the kidney. 

P. Guttmann has recognized bromine in the contents of the acne pustules of 
bromism; Bill detected the bromide in marked quantities in the feces of men taking 
it; and H. Quincke found that when forty grains of sodium bromide were given 
to dogs with intestinal fistula, two and a half hours afterwards the intestinal juices 
were free from the bromide, which reappeared in them three to six hours later. The 
salt lias been found by Voisin, Amory, Namias, Bill, etc., in the saliva and in the 
urine, and by Amory in the perspiration. In the body of a man who died while 
taking it, M. Namias found it in all the liquids, as well as in the brain, liver, spinal 
cord, lungs, etc. The rapidity of elimination seems to vary: thus, Amory recovered 
one-half of the amount ingested during the first, and one-third during the second, 
twenty-four hours, and Ware (Thesis of H. P. Bowditch) obtained a little more 
than half of the amount ingested in the urine of the succeeding thirty-two hours, 
while Bill was not able to get more than one-eighteenth of it during the first day. 
Bill has frequently found the bromide in the urine two weeks after the last dose 
has been exhibited; and Rabuteau has seen its presence persist under similar circum- 
stances for a month. According to T. Hondo, when the diet is rich in sodium chloride 
the bromides are eliminated much more freely than when common salt is withheld. 

When a bromide is given continuously it accumulates in the body 
and may be found in every tissue, but, according to Doyon and 
Cazeneuve (confirmed by Fere and Herbert), it is stored up in the 
nerve-centres much more largely than elsewhere. 

Physiological Action. — The bromides in sufficient concentration 
are poisonous apparently to all forms of animal protoplasm. They 
show, however, a selective action upon the nervous system. 

Nervous System. — In man and the higher mammals the first action 
of the bromides is upon the brain, in which they seem to depress both 
the intellect and the psycho-motor areas. After larger doses there is 
also depression of the spinal cord. In the frog the bromides give a 
loss of reflex power at a time when voluntary motion persists, indicat- 
ing that their first action in these animals is upon the sensory side 
of the spinal cord. In larger quantities there is also depression of 



DKPRKSSO-iMOTORS L55 

the motor tracts in the cord. It is probable also that in these animals 
there is a depression of the sensory nerve-endings. That a large dose 
is capable of affecting the sensory system in man, as well as in the 
frog, is shown by the tact that in several cases more or less complete 
general cutaneous anesthesia has followed the ingestion of the bromide. 

Potassium bromide administered to frogs in minute doses produces as a first 
result a tetanoid condition, in which there may be very marked opisthotonos. 
After a short time this stage of muscular excitement gives way to one of great 
muscular relaxation and total abolition of reflex actions. Voluntary movements, 
however, often occur during this period, and the frog which has been lying limp 
and apparently dead will startle the observer by a sudden vigorous leap. This 
fact has been so frequently witnessed that there can be no doubt of its truth.* 
Very early in the paralytic stage the respiratory movements are affected, and 
they gradually grow less until their final arrest. Upon mammals (Eulenbcrg and 
Guttmann) the bromide acts very much as upon frogs, inducing progressive paraly- 
sis, depression of temperature, and death by asphyxia when given in small 
poisonous doses; and great disturbance of the circulation, with finally diastolic 
arrest of the heart, when very freely administered. 

The persistence of voluntary movement in the frog after the abolition of reflex 
actions shows that the influence of the drug is not chiefly exerted upon the cerebral 
centres of motor impulse, nor upon those cells of the cord which originate movement, 
but upon either the afferent nerves or those portions of the cord which transmit the 
impulse from these nerves to the cells presiding immediately over motion. Both 
Lewisky and Purser found that death occurred from small doses before the motor 
nerve-trunks and the muscles had lost their irritability (confirmed by Saisson). 
This being so, the question arises whether the paralysis be spinal or due to paralysis 
of the peripheral afferent nerves. There is an apparent conflict in the evidence 
upon this point. Eulenberg and Guttmann found that when access of the poison 
was prevented to one or more limbs by tying the arteries, reflex actions were abol- 
ished in these parts as rapidly as in others. Similar results have been obtained by 
Lewisky, by Roberts Bartholow, by Purser, and by Laborde. On the other hand, 
Damourette and Pelvette assert a contrary result. Unfortunately, they do not 
give the details of their experiments. They state, however, that if the lumbar plexus 
of vessels be tied before the poisoning, the fore feet lose their reflex activity before 
the hinder. It seems well established that cutaneous anesthesia in greater or less 
degree accompanies the loss of reflex activity; for, as Purser says, a poisoned animal 
quite able to jump submits to pinching, pricking, burning, etc., without moving. 
Eulenberg and Guttmann have seen the same thing in some rabbits. Damourette 
and Pelvette have noticed a condition in which electrical stimulation of a nerve- 
trunk produced marked reflex action, although no excitement of the skin supplied 
by the afferent fibres of the nerve was capable of doing this, showing that' the 
extremities of the sensitive nerves are affected before the trunks. The evidence 
is, we think, sufficient to prove that the bromides affect all parts of the nervous 
system of the lower animals, but that the cerebrum, the motor tract of the cord, 
and the efferent nerves are the last portions to be affected; that the most sensitive 
to its action is the receptive portion of the cord, — that which receives and trans- 
mits reflex impulses, — and next to this, and perhaps almost equally susceptible 
with it, are the peripheral ends of the afferent nerves. 

Upon the cerebrum of the higher animals the bromides undoubtedly exert an 
influence, and the researches of Albertoni have thrown much light upon the useful- 
ness of the drug in epilepsy. That observer found that when administered to dogs 
the bromide depresses very markedly the power of the motor zone of the cerebral 
cortex to respond to stimuli, and to give forth, on decided irritation, epileptic dis- 
charges; it was also discovered that this action of the bromide was much more 

* It is vouched for by the following observers: J. M. Purser, Lewisky aus Kazan, ,T. V. 
Laborde, Damourette and Pelvette. 



156 GENERAL REMEDIES 

decided when there had been a prolonged saturation of the system with the drug 
than after a single large or even toxic dose. According to the researches of A. 
Crisafulli, the action of the bromides upon the cells of the cerebral cortex is so power- 
ful that vacuolization and other demonstrable changes are produced by it. The 
intellectual symptoms of bromism show that in man the action of the bromide on 
the cerebral cortex is more marked than in the lower animals, on account, no doubt, 
of the higher cerebral development. The drug in other respects acts upon man as 
upon lower mammals, lowering the reflex excitability of his spinal cord, paralyzing 
the ends of the peripheral nerves, etc. 

According to the researches of B. Schulze, there is under the influence of the 
bromide a decided decrease in the elimination of phosphorus, — an indication that 
the protoplasmic molecular changes in the nervous system are lessened by the drug. 

Circulation. — The experiments of J. G. Schouten and others have 
shown that potassium bromide when given in large doses lowers 
the blood-pressure by weakening the heart. This effect is, however, 
probably to be attributed to the potassium rather than to the 
hydrobromic acid. In the physiological studies of E. T. Reichert, 
hydrobromic acid was found to produce a temporary elevation of the 
blood-pressure, which was attributed, without proof, to vaso-motor 
spasm of peripheral origin. Large doses were directly paralyzant 
to the heart. 

Temperature. — In warm-blooded animals, toxic doses of potassium 
bromide lower very decidedly the temperature. There have been 
no calorimetric experiments to determine whether this fall of tem- 
perature is due to a diminished heat-production or an increase in 
heat-elimination. 

Nutrition. — The symptoms of bromism show that hydrobromic 
acid has a distinct influence upon the general nutrition. The experi- 
ments of Schulze, Chittenden and Culbert seem to show that bromides 
increase the excretion of urea but diminish the output of phosphorus. 
Rabuteau on the other hand in a single experiment found that the 
elimination of urea was slightly diminished by potassium bromide. 

SUMMARY. — When in sufficient concentration hydrobromic 
acid acts as a powerful depressant upon all of the higher tissues. 
It is absorbed rapidly and eliminated in all the secretions more 
slowly; so that when given continuously it accumulates and 
causes bromism. The portions of the human organism most sensi- 
tive to its influence are the whole cerebral cortex, the receptive 
side of the spinal cord, and the afferent peripheral nerve-endings. 
The influence of the bromides upon the circulation is subordinate to 
its action on the nervous system. 

Therapeutics. — The bromides are employed by the therapeutist 
to quiet cerebral excitement when not inflammatory in its nature; to 
lessen over-susceptibility of the spinal centres of reflex action, or of 
the peripheral afferent nerves which lead to these centres; and to 
subdue nervous excitement of the genital system. 

The bromides are contraindicated by an excessive irritability of 
the gastro-intestinal mucous membrane; when such condition exists 
they may provoke exhausting diarrhoea. Great exhaustion, and 



DEPRESSO-MOTORS 157 

especially great nutritive exhaustion of the nerve-centres, is a contra- 
indication to their use. Thus, owing to the excitement that attends 
confusionai insanity, — i.e., the insanities following child-birth, typhoid 
fever, surgical operations, etc., — bromides are frequently administered 
in large doses, to the great detriment of the patient. We are well 
convinced that under such circumstances they greatly lower the 
nutrition and check recovery. In the same way, in cerebral softening, 
senile dementia, and allied disorders, they must be used, if at all, 
only with the greatest reserve. 

There are various forms of nervous excitement, or unrest, such as 
sometimes follow excessive intellectual toil, anxiety, and other nervous 
.strain, or occur during convalescence from acute disorder, in which 
the salt now under consideration is very valuable. The same may be 
said of some forms of hysteria. In some cases of neuralgia the bromide 
affords great relief, but in the majority of cases it fails. It has seemed 
to us useless in neuralgia dependent upon anemia or want of power; 
and our experience agrees with that of Anstie, that it is especially 
useful in persons of good nervous power, muscular force, and activity 
of circulation. As an hypnotic, it is employed in wakefulness from ner- 
vous excitement and in delirium tremens, but is of very feeble power. 

The chief use of hydrobromic acid is to lessen motor activity. It 
is especially in epilepsy that it has attained a well-deserved reputation, 
doing far more good than all other remedies combined, sometimes 
apparently effecting cures, more commonly ameliorating the symp- 
toms, but occasionally failing entirely. There is no known method of 
distinguishing before trial with any certainty in what cases it will 
do good. The assertion of Trousseau, that it is least efficient in the 
mild form of the disorder known as petit mal, accords with our experi- 
ence. The most brilliant results have, as a rule, been obtained in 
cases of not too long duration in which the fits were frequent and 
severe. The governing principle in its use is to try it in every case, 
increasing the dose until a mild degree of bromism is induced, and 
being guided by the results. 

The drug is also often efficacious in various reflex spasmodic 
neuroses: in the vomiting of pregnancy or of uterine diseases; in the 
gastric convulsions of children; and, according to J. T. Rothrock, in 
preventing the so-called urethral fever induced in very susceptible 
males by the introduction of the catheter or bougie, it is very useful. 
The physiological action of the salt seemingly indicates that it is one 
of the remedies best suited for the treatment of tetanus. Clinical 
experience certainly accords with this conclusion: in a table pub- 
lished in previous editions of this treatise were collected thirty-four 
cases of tetanus, nearly all traumatic, treated chiefly by potassium 
bromide, with but four deaths. Not less than a half-ounce of the 
salt should be exhibited in the day, and at night hydrated chloral 
should be used as an hypnotic. 

In strychnine-poisoning, Saisson has demonstrated the value of 
the bromide by experiments on animals, and Charles B. Gillespie 



L58 GENERAL REMEDIES 

and C. L. Bard have each reported, under its use, recovery without 
vomiting after the ingestion of three grains of the alkaloid. 

In nervous excitement connected with the genital function, the 
bromide is often of value. When there is actual inflammatory disease, 
as in gonorrhoea, the drug frequently fails to effect the desired end. 
If, however, there be no organic lesion of the organs or of their nerve- 
centres, the continued dose will usually succeed to a greater or less 
extent. We have found the remedy effective in cases of semi-impo- 
tence from over-irritability of the organs causing emission too soon 
during attempted sexual congress. There is abundant evidence as 
to its value in nymphomania. As an adjuvant to other physical and 
moral measures of relief, the salt may be used with satisfaction in 
men suffering from masturbation. In nervous symptoms occurring 
at the time of the menopause or complicating uterine disease, and 
in the peculiar train of morbid phenomena arising from the forced 
suppression of the sexual function in vigorous individuals of either 
sex to whom circumstances have denied marriage, the bromides have 
almost a unique power. 

Bernard affirms that potassium bromide in doses of from twenty 
to forty-five grains a day removes with marvellous quickness malarial 
enlargements of the spleen. 

Administration. — The action of bromine, whether combined with 
hydrogen to form hydrobromic acid, or with a base to form a bro- 
mide, is always the same, but the action is more or less modified 
according to the physiological effects of the base with which it is 
combined; thus, potassium having marked depressant action of itself 
upon the central nervous system, the potassium bromide is the most 
actively depressant of these salts. The ammonium radical is stimu- 
lating in its effect upon the spinal cord and therefore this salt is less 
useful as a spinal depressant than almost any- other official bromide. 
Also the activity of the bromides probably bears a relation to the 
percentage of bromine in their composition; it is interesting to note 
therefore that calcium bromide contains eighty per cent, of bromine; 
sodium about seventy-seven per cent.; potassium salt about sixty- 
seven per cent., and the strontium bromide, sixty-five per cent.; 
a fluidrachm of the dilute hydrobromic acid is equivalent to about 
8 grains of sodium bromide. For general purposes the sodium bro- 
mide is probably the salt of preference, although frequently the best 
results are obtained by combining several of the bromides. 

When the bromides are used in chronic conditions it must be borne 
in mind that on account of their comparatively slow elimination there 
is a marked tendency for them to accumulate in the system and that 
therefore when used over long periods of time they must be given in 
much smaller doses than when used in a single dose. While it is 
perfectly safe to give one or two drachms of sodium bromide or even 
more at a single dose, in diseases of prolonged duration such as epi- 
lepsy this quantity cannot be exceeded in the twenty-four hours 
without danger of unpleasant symptoms. The action of the bromide, 



DEPRESSO-MOTORS L59 

as already mentioned, in the human being is less depressant upon 

the spinal cord than upon the brain, therefore, when this drug is 
used in the treatment of spinal convulsions such as tetanus or 
strychnine-poisoning, it is necessary to give very large quantities. 
In tetanus two to three drachms should be administered every two 
or three hours. 

On account of the irritant action upon the stomach the bromides 
should always be given well diluted. 

Toxicology. — So far as we know, no fatal case of acute poisoning 
by potassium bromide is on record. In our own experience an ounce 
taken by mistake by a young adult produced violent pain in the 
oesophagus, nausea with a little vomiting, great thirst, feeling of 
weight in the head, and excessive sleepiness, which lasted for three 
days. In a case reported by Dougall an ounce and a half taken within 
twenty-four hours was followed by coma, with weak pulse, cold ex- 
tremities, temperature 96.8° F., total abolition of the reflex action, 
and general cutaneous anesthesia, followed by excessive drowsiness 
interrupted by periods of talking delirium and by periods of rationality, 
the symptoms gradually subsiding during a fortnight. 

From the continuous employment of large doses of the bromide, 
however, when it is taken with sufficient freedom to accumulate in 
the system, a conjunction of phenomena known as bromism arises.* 
The cerebral symptoms are a sense of mental weakness, heaviness of 
intellect, failure of memory, partial aphasia, great somnolence, and 
depression of spirits. With these there may be decided impairment 
of the sensibility of the mucous membranes and of the skin, so that 
titillation of the fauces may be without effect, and, according to 
Puche, even heat applied to the skin calls forth no complaint; Huette 
has seen in some cases absolute anesthesia of the sclerotic conjunctiva. 
The sexual function is abolished. There are also very generally fetid 
breath and an eruption of acne which may indeed be very severe. 
Of course, in any individual case of bromism many of these symptoms 
may be wanting; but when the use of the remedy is persisted in, 
they all at last become developed in an intense degree. In the words 
of Edward H. Clarke: 

"The fetid breath becomes nauseous; oedema supervenes on congestion of the 
uvula and fauces; the whispering voice sinks into aphonia; sexual weakness de- 
generates into impotence; muscular weakness becomes complete paralysis; reflex, 
general, and special sensations disappear; the ears do not hear, nor the eyes see, 
nor the tongue taste; the expression of hebetude becomes first that of imbecility, 
then that of idiocy; hallucinations of sight and sound, with or without mania, pre- 
cede general cerebral indifference, apathy, and paralysis; the respiration, without 
the stertor of opium or alcohol, is easy and slow; the temperature of the body is 
lowered; as the bromism becomes more profound, the patient lies quiet in bed, 
unable to move or feel or swallow or speak, with dilated and uncontractile pupils, 
and scarcely any change of the color of his skin or face. " 

* F<Srd asserts that many of the disagreeable symptoms of bromism are due to its disturbance 
of the alimentary canal, and are prevented by the daily exhibition of four grammes of betanaphthol 
and four grains of bismuth salicylate, which doses are borne for months without any inconvenience, 
usually with much benefit to the appetite and digestion {Nouv. Iconog. de la Salpkr., 1890). 



160 GENERAL REMEDIES 

Death has been attributed to the continuous use of the bromide 
in large doses. Thus, Hameau reports the case of a young woman 
who took four and a half pounds during the course of ten months, 
and while in a condition of cachexia, with yellowish skin, a copper- 
colored eruption upon the forehead, colic, gastralgia, insomnia, etc., 
suddenly became greatly prostrated, and had delirium with profuse 
sweats, followed by death in four days. Anton Eigner details the 
case of a woman who took five pounds in less than a year, and while 
having very pronounced symptoms of bromism was seized with de- 
lirium and suffered from hallucinations of sight and hearing, saying 
that she was being poisoned, and finally died of pneumonia. In 
neither of these cases can it be considered probable that the bromide 
was the direct cause of death. 

The symptoms of bromism usually disappear promptly with the 
withdrawal of the drug and leave behind no unpleasant sequels. 
Apparently the use of arsenic greatly lessens the liability to acne and 
it is frequently well, therefore, when using the bromides over long 
periods of time, to add one or two minims of the solution of potassium 
arsenite to each dose. 

Bromoform. — Bromoformum. — Formyl Bromide. — This is a colorless liquid 
with an ethereal odor and sweetish taste, which, first brought forward in 1849 by 
Nunneley and Schuchard as an anesthetic, was found too dangerous for use as such, 
but has been employed to a considerable extent internally in the treatment of 
whooping-cough, and other diseases for which the bromides are used. It is probably 
broken up in the system, but its products are eliminated with great slowness. It 
is undoubtedly capable of acting like the bromide, but has no advantage over the 
older preparations and is distinctly more dangerous. W. Gerhardi* has shown 
that bromoform is capable of producing wide-spread fatty degeneration in the 
lower animals. E. Kiwull has collected twenty cases of poisoning by it; the symp- 
toms have been pallor, titubation, dilatation of the pupil, coma, heart -failure, and 
collapse. The dose for the adult is six or seven minims (0.4 C.c.) in capsules. 

Two substances, apparently parallel in that they are saturated solutions of 
bromine in oil and in that the bromine is stated to be in combination with olein, 
have been put upon the market by manufacturers, and are probably identical in 
their physiological influence. 

Bromolein is a clear, yellow, oily liquid, said to contain twenty per cent, of 
bromine in oil of sweet almonds. 

Bromipin is a similar liquid, prepared with bromine and sesame oil, and sup- 
plied to the market by the manufacturers in two strengths, one containing ten, the 
other thirty-three and one-third per cent, of bromine. 

According to Merck's report, thirty grains of the stronger bromipin are equal 
to fifteen grains of potassium bromide; so that thirty grains of bromolein should be 
considered about equal to ten grains of potassium bromide. Of the weaker bromi- 
pin one-half ounce may be given as dose to the adult, representing theoretically 
twenty-four grains of bromide. 

These substances may be used hypodermically, or may be employed, diluted 
with oil, endermically. After either method of administration bromine soon appears 
in the urine. They have been recommended by various clinicians in epilepsy, insom- 
nia, neurasthenia, and other diseases in which the bromides are commonly em- 
ployed. The dose of either substance appears to be in direct proportion to the 
amount of bromine contained. 

* See also Wien. Med. Jahrb.. 1883, 497. For poisoning, see Times and Register, 1892; also 
Annals of Gynecology, 1890-97; Pest. Med.-Chir. Presse, 1897. 



DEPRESSO-MOTORS 161 

Monobromated Camphor. -Camphara Monobromata. — This is a compound in 
which one atom of hydrogen in the camphor has been replaced by bromine. It 

occurs us a crystalline solid, or in large aeicular crystals several inches long. 

Our present knowledge of the physiological properties of broinated camphor 
rests upon the work of Bourneville, of Lawson, of Pathault, of Richard Peters, 
and of Pellicani. In frogs there is progressive loss of reflex excitability and of 
voluntary movement (Peters), which, according to Pellicani, is due to paralysis of 
the motor nerves. Death is caused by arrest of respiration (Peters). In mammals 
it produces violent convulsions, muscular weakness passing almost into paralysis, 
reduction of temperature (after small doses preceded by a rise — Peters), great- 
decrease in the rate of the respiration and of the pulse (with occasional periods of 
hurried respiration — Peters), profound sleep or stupor, and finally death. Bourne- 
ville states that the blood-vessels of the eyes and ears are diminished in calibre. 
Upon man the drug probably acts as upon other warm-blooded animals; in a 
case reported by M. Rosenthal, forty-five grains of it caused tremblings, marked 
slowing of the pulse, and coma of six hours' duration. 

Bromated camphor was first introduced by Deneffe as a nervous sedative, and 
as an antispasmodic, especially in delirium tremens, but is of little value; it is still 
used in hysteria, and has an especial reputation in sexual excitement and spermator- 
rhoea. It is taken with difficulty, and is likely to irritate the stomach. It is too irri- 
tant for hypodermic use. Dose, five to ten grains (0.3-0.6 Gm.), in capsule or 
coated pill, and repeated as necessary. 

For a resume of the physiological action of bromal hydrate, which 
is certainly valueless as a practical medicine, see the tenth edition of 
this treatise. 

NITRITES. 

Although nitrous acid is itself not used in medicine all its salts 
as far as known have similar physiological properties.* Apparently 
also the combinations formed by nitric acid and the polyatomic 
alcohols exercise the same effect upon the economy, probably being 
reduced in the system to nitrites. Four drugs belonging to this group 
are recognized by the U. S. Pharmacopoeia. 

Amyl nitrite is a yellowish oily liquid, extremely volatile, with a 
characteristic fruity odor, which results from the action of the nitric 
acid upon amyl alcohol. The Pharmacopoeia directs that it contain 
about eighty per cent, of amyl nitrite. f 

Sodium nitrite (this should be carefully distinguished from sodium 
nitrate) occurs in the market usually in white pencils; it has a mild 
saline taste and when exposed to the air deliquesces and is gradually 
oxidized into the nitrate. It is freely soluble in water. 

Ethyl nitrite is official in the form of a four-per-cent. solution 
(spiritus eetheris nitrosi). This is a volatile inflammable liquid of a 
pale yellow color with a fragrant ethereal odor. 

Glyceryl trinitrate or nitroglycerin, although being a salt of nitric 
acid, affects the system similarly to the salts of nitrous acid, probably 

* For evidence as to the physiological unity of the nitrites see G. A. Atkinson, K. T. Reichert 
i -odium nitrite), Richardson, Leech (ethyl nitrite), Brunton and Tait, Murrell and Hay, Henocque 
(nitroglycerin). 

t Berloni's ether or tertiary amyl nitrite, a mixture of amyl nitrite and iso-butyl nitrite, has been 
found by Lauder Brunton and T. J. Bokenham to act very much as does the ordinary amyl nitrite, 
except that its effects are somewhat more slowly developed and are more permanent. It is not 
proved to be more stable than the ordinary amyl nitrite and has no advantages over the latter. 
According to Dunstan, amyl nitrite of commerce is chemically a mixture of a and /3 amyl nitrites, 
ISO-butyl nitrite, ethyl nitrite, and propyl nitrite {St. Bartholomew's Hospital Report, 28, 1892). 
11 



162 GENERAL REMEDIES 

being reduced in the body. It is official in the form of a one-per-cent. 
solution. Tablets of nitroglycerin, although not official, are largely 
employed. They are very likely however, to contain much less of the 
nitroglycerin than stated in the label, as this principle, being volatile, 
is largely evaporated unless they are carefully protected. 

The nitrites are incompatible with antipyrine, the iodides, the 
bromides and ferric sulphate. 

Official Preparations: 

Amylis Nitris 1 to 5 minims (0.06-0.30 C.c). 

Sodii Nitris 1 to 3 grains (0.06-0.20 Gm.). 

Spiritus iEtheris Nitrosi (4 per cent. Ethyl 

Nitrite) 30 to 90 minims (2-6 C.c). 

Spiritus Glyceryls Nitratis (1 per cent. 

Nitroglycerin) 1 to 3 minims (0.06-0.18 C.c). 

Local Action. — The nitrites are practically without irritating 
properties. They cause a progressive loss of functional power in every 
highly organized tissue with which they come in contact. Nerve- 
centres, peripheral nerves, muscles of organic and voluntary life, all 
succumb to them alike. If the contact be not continued too long, the 
tissue may recover even after a total suppression of its function, — a 
proof that the poison exerts no destructive chemical or devitalizing 
influence upon the tissues, such as that of sulphuric acid or veratrine. 

Absorption and Elimination. — Amyl nitrite is absorbed with 
extraordinary rapidity, especially through the lungs, and must also 
be eliminated from or destroyed in the system with great rapidity 
on account of the fugaciousness of its action. F. Rohrmann believes 
that the nitrites undergo oxidation in the system, because he has 
found that when potassium nitrite is administered to the lower animals 
it appears in the urine as potassium nitrate. 

Physiological Action. — The most prominent symptoms induced 
when amyl nitrite is inhaled by a man in moderate quantities are a 
sense of great fulness and distention of the head, amounting at last 
to severe pain, and accompanied by intense flushing of the face, a 
deep, labored respiration, and an exceedingly rapid, violent action of 
the heart. The succession of these phenomena is usually so rapid that 
often they seem to be simultaneous; but it is said that the cardiac 
disturbance is sometimes very distinctly manifest before the other 
symptoms. It has been noticed by Peck and confirmed by Ladendorf 
that objects look yellow to a person fully under the influence of the 
drug. After poisonous doses the symptoms have been great pallor, 
usually dilatation but sometimes contraction of the pupils, excessive 
muscular relaxation, slow, scarcely perceptible pulse, hemoglobinuria, 
and irregular respiration. 

In the lower animals the first stage of the action is like that just 
described in man. After this the breathing becomes violently hurried 
and panting, progressive muscular weakness and diminution of reflex 
activity ensue, and finally death from failure of respiration, sensation 
and consciousness being preserved almost to the last. A very peculiar 



DEPRESSO-MOTORS 163 

symptom is that a long time before death both the arterial and the 
venous blood become of a nearly uniform chocolate color. Con- 
vulsions are sometimes present; but in our experience more often the 
animal is exceedingly quiet throughout the poisoning. 

Nervous System. — The influence of the nitrites upon the cerebrum 
is very feeble, disturbances of intellection and of consciousness not 
being produced except by very decided toxic doses, and not being 
prominent symptoms of the poisoning. As was shown by H. C. Wood, 
the lessening of reflex activity and of voluntary motion which undoubt- 
edly occurs in toxemia from these drugs is chiefly spinal in its origin, 
since after death the nerves and muscles preserve, though in an 
impaired condition, their functional power. On the motor centres 
of the cord the nitrite acts as a direct and powerful depressant, at 
the same time that it exerts a similar but much less pronounced in- 
fluence on the nerves and muscles, decreasing, but not destroying, 
their functional life. The diminution of reflex activity is never pre- 
ceded by a stage of functional excitement. In some animals con- 
vulsions do occur after amyl nitrite; but they are in all probability 
cerebral, not spinal, and due to the asphyxiating influence of the 
poison. Over the sensory nerves and centres the nitrites have but 
little power. They are among the last portions of the body to be 
affected, sensation being intact until near death: so that the drug is 
in no sense an anesthetic. 

Respiration. — It is certain that the respiratory centres are greatly 
depressed by full doses of the nitrites, the breathing becoming both 
slow and shallow, and death finally occurring from centric paralytic 
asphyxia. Mayer and Friedrich assert that small doses of amyl 
nitrite increase the rapidity and depth of respiration by stimulating 
the respiratory centres; but this remains at present doubtful, it being 
probable that the increased respiration is secondary to the disturbance 
of the circulation, as is asserted by Winkler. 

Circulation. — Although the pulse may be much increased in fre- 
quency sometimes from the very beginning by amyl nitrite, the 
arterial pressure is diminished, and finally is reduced almost to zero, 
the fall of pressure occurring equally after section of the vagi as at 
other times. As the number of heart-beats in the uninjured animal 
is increased rather than diminished, while the strength of the indi- 
vidual beat is not perceptibly lessened, it is evident that, at least in 
the early stages of the poisoning, the diminution of arterial tension 
is not cardiac in origin, but must be due to dilatation of the capillaries. 

This conclusion has been confirmed by numerous experimenters.* 
Although the question whether this vascular paresis is centric or 
peripheral cannot be answered definitely the effect is probably a 
direct action on the arterial walls. 

* According to Bradford and Dean (J. P., 1894, xvi. 34) and H. C. Wood, Jr. (A. J. P., 1902, 
vi. 283) the nitrites cause a rise of pressure in the pulmonary circulation. The explanation of this 
phenomenon involves the disputed physiological question of the existence of a pulmonary vaso- 
motor system and cannot therefore be taken up here. 



Kit 



G i:\EliAL REMEDIES 



Concerning the action of the drug upon the heart-muscle evidence 
is not convincing; although certain observers have claimed to have 
found some increase in the working power of the isolated frog's heart 
after small doses of the nitrite, others have failed to obtain evidence 
of such stimulation. If there is any direct stimulant influence upon 
the heart it is extremely slight, and only occurs after small doses; 
large quantities certainly depress the cardiac muscle as well as the 
vaso-motor system. The increase in the pulse-rate is owing to a 
paralysis of the cardio-inhibitory centres in the medulla. 

That the fall of pressure is of vascular origin is shown by an experiment of 
Brunton, who found that if the descending aorta were tied high up, no perceptible 




Fig. 11. — Showing Effect of Sodium Nitrite on the Circulation. 

It lowers the pressure by dilating the vessels and increases the pulse-rate by paralyzing the 
cardio-inhibitory centres. Time marker indicates 5 seconds. 



fall of pressure was produced by the inhalation of the amy] salt until very late in 
the poisoning, when the heart itself was acted upon by the drug; also by the fact 
noted by Amez-Droz and by Gaspy, that the vessels of the rabbit's ear and of the 
frog's web can be seen to dilate when the salt is inhaled. In man the flushing 
of the face and of the retina, as noted by Charles Aldridge, indicates that the 
nitrite acts locally, probably upon some centre, before it does generally, as general 
dilatation of the vessels causes pallor. 

An interesting question which here arises is, whether the dilatation is centric, 
due to an action on the vaso-motor nerve-centres, or peripheral, due to a direct 
action on the muscular coat of the arterioles. We believe that it must be peripheral, 
and not centric, in its origin, since in the experiments both of Brunton and of H. C. 
Wood it occurred after the arterioles had been separated from the vaso-motor 
centres by division of the cord. 

Atkinson and D. J. Leech have each found that the nitrite enormously increases 
the flow of blood-serum which is being forced by a steady pressure through the 



DEPRESSO-MOTORS L66 

decapitated tortoise, or through a recently excised kidney; a solution 1 in 10,000 
had a distinct effect in widening the blood-paths, In conclusion, it seems to us 
established that amyl nitrite does act locally on the coats of tho arterioles, although 
it may at the same time influence the vaso-motor centres. 

Bernheim, however, asserts that this cannot be so, and that the dilatation must 
In- solely due to an action upon the vaso-motor centres, because he found that gal- 
vanization of the cervical sympathetic still caused contractions in the vessels of the 
ear of a rabbit to which amyl nitrite had been given. As pointed out by Pick, 
Bernheim's experiment does not warrant his conclusion. It only shows that the 
muscle-fibres in the walls of the vessels are not so completely paralyzed as to be 
unable to respond to very powerful stimuli. W. Filehne also dissents from the 
view that the action of the nitrite is upon the vessels. Filehne affirms that when 
to animals, whose lungs are exposed, inhalations of the nitrite were given, the change 
of color was not nearly so great as in the ears, and that if the sympathetic had been 
destroyed in the neck of a rabbit, and amyl nitrite exhibited, the vessels on 
the unwounded side actually became larger than those of the opposite ear. The 
answer to these results is, that opening the chest must derange most profoundly 
the pulmonic circulation, and that all observations upon the comparative size of 
vessels are very apt to be mere guess-work when the change is slight. Moreover, 
in Sehuller's experiments, after destruction of the cervical sympathetic in a rabbit, 
inhalations of the nitrite produced still further dilatation of the vessels of the ear. 

Filehne has by a single very ingenious experiment apparently shown that the 
acceleration of the pulse is due to a depressing influence upon the inhibitory centres. 
He divided the par vagum in a rabbit, employed an electric current to the severed 
nerves of sufficient strength to bring the pulse-rate to normal, and found that the 
nitrite was powerless to affect the rapidity of the cardiac action. Certain experi- 
ments performed by Mayer and Friedrich confirm that oj Filehne. It is known that 
sudden asphyxia slows the pulse by exciting the inhibitory centre. Mayer and 
Friedrich found that this action is prevented by the inhalation of the amyl nitrite. 
Then, again, they found that when by compression of the arteries the blood was 
prevented from going to the head, the nitrite did not increase the rapidity of the 
pulse, and also determined that the reflex inhibitory slowing of the heart by irrita- 
tion of a sensitive nerve is prevented by amyl nitrite. The sudden, thumping action 
of the heart which is, in man, so prominent a symptom of nitrite action is therefore 
probably, at least in part, due to depression of the inhibitory apparatus. There 
is, however, as pointed out by Reichert, some reason for believing that in small 
doses the nitrites act primarily as stimulants to the heart. Lauder Brunton long 
ago discovered that if the aorta be compressed so as to eliminate in great part the 
influence of the vaso-motor system, the nitrite causes a primary rise in the arterial 
pressure; and it is perfectly possible for an excessive heart-action to be more than 
neutralized, so far as the arterial pressure is concerned, by a vaso-motor depression, 
so that the immediate fall of pressure caused in the normal animal by the nitrite is 
not proof that the heart may not be stimulated. In G. A. Atkinson's experiments, 
1 part of amyl nitrite in 20,000 produced a slight increase in the working power of 
the cut-out frog's heart (Williams's apparatus); 1 in 10,000 caused a rise for four 
or five minutes, followed by a fall; smaller and larger amount than these had either 
no effect or lessened the heart's action.* It seems, therefore, that our present 
physiological evidence justifies the belief that very small quantities of the nitrites 
primarily stimulate the heart, although it is demonstrated that in moderate or large 
amounts the drug depresses or paralyzes the heart-muscle. 

Urine. — F. A. Hoffmann found that in the rabbit a hypodermic 
injection of 0.111 to 0.113 gramme of amyl nitrite is enough to cause 
diabetes. If twice this amount of the amyl salt is used, the sugar 

* There is, however, still much uncertainty about the matter. D. J. Leech affirms that 1 in 
10,000 always quickens and weakens the beat of the isolated frog's heart in a Roy apparatus. In 
a si.igle experiment made with amyl nitrite on the isolated mammalian heart, Bock came to the 
conclusion that the amyl nitrite has no effect upon the heart itself. The experiment, however, 
does not seem to us sufficient, and the method employed is open to very grave objection. 



166 GENERAL REMEDIES 

becomes very abundant in the urine, and continues to be present for 
from twelve to thirty hours. Consentaneously with the elimination 
of sugar there is a great increase in the amount of the urine. The 
occurrence of glycosuria in man has not been recorded; it is produced 
by toxic doses only, if at all. 

Temperature. — The nitrites, if given in sufficient amount, reduce 
most remarkably animal temperature. We have seen a pigeon per- 
fectly conscious although its temperature had been brought down 
by this agent some 13° F. This influence is as marked in fever as in 
the normal condition of the animal, and is independent of the nerve- 
centres, occurring after section of the cord, and even after death in 
those cases in which post-mortem rise or continuance of high tempera- 
ture normally takes place. We have also experimentally determined 
that it is associated with diminished excretion of carbonic acid. It 
must therefore be due to a direct arrest or check of tissue-changes or 
oxidation within, or without, the blood. This is probably connected 
with the changes caused by the nitrites in the hemoglobin. After 
large doses of the nitrites the blood in both arteries and veins assumes 
a uniform chocolate-brown color. This is due to the formation of a 
new chemical compound, probably methemoglobin. This substance 
is a much more stable body than oxyhemoglobin, that is, it gives up 
its oxygen much less readily to the tissues. Although the oxygen- 
carrying power of the blood is much reduced in nitrite-poisoning, 
Gamgee has shown that it is not entirely lost, nor are the corpuscles 
of necessity permanently injured. The mouth-temperature in man 
is certainly sometimes elevated by the inhalation of amyl nitrite, but 
the rise is a very temporary one. W. A. Manassein and N. Sassezki 
found, in a number of studies upon normal and fevered men, that 
while the peripheral temperature was at first increased the rectal 
temperature was always reduced, and after a time the surface of the 
body grew cooler. The maximum reduction was reached in one to 
one and a half hours, and in a case of fever amounted to 3° C. 

The first to describe the chemical changes in the blood was Gamgee. He be- 
lieved the new compound to be a nitrite-oxyhemoglobin, but it has been considered 
by most observers, on account of similarity of spectrum, to be the methemoglobin 
of Hoppe-Seyler. Haldane, Makgill, and Mavrogordato assert, however, that the 
spectra are not absolutely identical, and that the new compound is really a mixture 
of nitric-oxide-hemoglobin and hemoglobin. 

Gamgee showed conclusively that the new compound in the blood yields oxygen 
to a reducing agent, and that when nitrite blood is brought into contact with pre- 
pared guaiacum-paper it still oxidizes it, though not so actively as normal; so 
that evidently the blood-corpuscles retain to a greater or less degree their power 
of yielding ozone to bodies desiring it, and are capable of exerting at least this por- 
tion of their respiratory function: further, when this ozone is given up and the 
oxyhemoglobin changed into hemoglobin, so far as our present knowledge goes, 
the hemoglobin must absorb more oxygen before it can unite with the nitrite. Evi- 
dently, then, absorption of oxygen must take place; evidently the blood-corpuscles 
must perform their respiratory function; but evidently also they are greatly 
crippled and impaired in the rapidity and ease of its performance. 

Haldane, Makgill, and Mavrogordato found that when an animal is placed in 
oxygen gas, under a pressure sufficiently high to so saturate the serum of the blood 



DEPRESSO-MOTORS 167 

with oxygen that it (t ho serum') was able to maintain life, ordinarily fatal doses of 
the nitrites [ailed to kill, although l>y increasing the amount, of the nitrite death 
could be produced; evidence thai the influence of the nitrites upon oxidation is an 
important but not a sole factor in their toxic influence. Further, (Jamgee showed 
that potassium and other nitrates act upon the blood as do the nitrites, yet the 
symptoms caused by them are very different from those produced by the nitrites. 
It is also sure that various drugs in toxic doses check oxidation, but do not cause 
the same symptoms as are produced by the nitrites; finally, when arrest of oxida- 
tion in the body is caused by substituting oxygen by an inert gas, such as nitrogen, 
the symptoms are essentially different from those of nitrite-poisoning, the brain 
and consciousness being always affected before the spinal centres, whereas under 
the influence of amy] nitrite the contrary occurs. 

In sufficient dose amyl nitrite is poisonous to the white corpus- 
cles; Atkinson has found that 1 in 1000 kills the corpuscles in from 
fifteen to twenty minutes. 

SUMMARY. — The dominant physiological action of the nitrites 
is upon the spinal cord and the circulation. Under their influence 
arterial pressure falls from paralysis of the blood-vessels, chiefly 
due to a direct action upon the muscles in their walls. At the same 
time the vagi-centres are paralyzed and the heart is stimulated 
directly or indirectly, the number and force of its contractions being 
increased, this period of stimulation after moderate doses gradually 
subsiding into the normal state, but after toxic doses passing into 
one of cardiac paralysis, with a final arrest in diastole, ■which is 
due to a direct action upon the heart-muscle or contained ganglia. 
Paralysis of motion and loss of reflex activity, prominent phe- 
nomena of advanced poisoning, are due to a direct action upon the 
motor side of the spinal cord. Death results finally from paralysis 
of the respiratory centres. By a direct action upon the red blood- 
corpuscles the hemoglobin is converted into a new compound, prob- 
ably methemoglobin. The fall of the bodily temperature is probably 
the result of lessened oxidation. Locally applied in concentrated 
form, the nitrites paralyze all higher tissues. 

Therapeutics. — The nitrites are employed to meet indications 
which are very closely in accord with their known physiological action. 
When an extremely prompt but not lasting effect is desired amyl 
nitrite should be chosen. Thus by virtue of its antispasmodic effects 
it may be of service in certain forms of epilepsy. In a fully developed 
paroxysm of epilepsy it must be used with caution, because the 
patient's condition will obscure its early effects; but in the status 
epilepticus, when there is an almost indefinite repetition of the fits, 
the remedy may be of great use in stopping the convulsions. When 
there is a notable interval in ordinary epilepsy between the aura 
and the convulsion, the latter can usually, if not always, be entirely 
prevented : the patient should carry a small vial containing a few 
drops of the drug or so-called "pearls" (minute flasks, each con- 
taining five minims, which are to be broken in a handkerchief), and 
should inhale the amyl salt so soon as the aura is felt. 

S. Weir Mitchell calls attention to the value of the nitrite as an 
aid in diagnosing those occasional cases of nervous disorder in which 



16S GENERAL REMEDIES 

petit mal is simulated by attacks really due to passing congestion of 
the nerve-centres. He asserts that in these cases amyl nitrite instead 
of arresting the paroxysm increases its severity. 

In nervous spasmodic dysmenorrhea, it is stated by various authori- 
ties that inhalation of amyl nitrite will sometimes bring immediate 
relief, two to six minims being given when the pain comes on, and 
repeated pro re nata. As was first pointed out by William F. Jenks, 
the nitrite is most effective in arresting puerperal convulsions, but if 
the convulsions occur shortly after parturition the use of the nitrite 
is attended by the greatest danger of producing uterine relaxation 
and serious or even fatal post-partum hemorrhage. 

Amyl nitrite is a very valuable remedy in the treatment of tetanus 
and of strychnine-poisoning. In the experiments of St. Clair Gray, 
which have been substantially confirmed by Hobart A. Hare, although 
one-quarter of a grain of strychnine was found to be sufficient to 
cause death in an immediate convulsion in the rabbit, no decided 
symptoms whatever were induced in two rabbits by the subcutaneous 
injection into each of half a grain of strychnine with ten drops of the 
nitrite. During a paroxysm of cramp asphyxia from strychnine, the 
poison of tetanus, or other similarly acting cause, the nitrite should 
be given hypodermically, the lack of respiratory movement interfer- 
ing with its absorption through the lungs. In cases of uremia, or 
puerperal eclampsia one of the more persistently acting salts, as 
nitroglycerin, should be chosen. 

During the algid stage of an ordinary intermittent fever amyl nitrite 
will put an end immediately to the chill, but does not affect the 
development of the hot stage. It might possibly be of service in the 
algid stage of a pernicious malarial fever. 

Led by the evidences of arterial spasm in the sphygmographic 
tracings in a case of angina pectoris, Lauder Brunton in 1867 suggested 
its use in that disease. As the pathology of these cases of heart-pang 
is not definitely made out, it seems useless to speculate how the nitrite 
acts in many cases; but there is abundant evidence of its value in 
relieving, almost instantly, agony which has resisted all other treat- 
ment. This appears also true whether valvular disease or merely 
functional disorder exists. Foster has found the drug of great service 
in aortic insufficiency with excessive hypertrophy and severe frontal 
headache. 

The nitrites, especially nitroglycerin, have been largely used in 
various forms of sudden heart-failure, even when such failure is depend- 
ent upon fatty degeneration or other disease of the heart itself. The 
direct stimulant influence, if it exist at all, of the nitrite upon the 
heart is, however, of the briefest duration, and if the least overdose 
of the drug be given, passes into cardiac depression. The zone between 
stimulation and depression of the heart is so narrow that the greatest 
care must be exercised whenever there is any cardiac disease, or 
whenever the heart is violently depressed by such a poison as chloro- 
form. Although Reichert states that he has seen the blood-pressure 



DEPRKSSO- MOTORS 169 

and pulse-wave, which had boon depressed almost to zero by ethylene 
bichloride, greatly increased by amyl nitrite, in an elaborate series 
of experiments made by H. C. Wood with chloroform no such effect 
could be obtained. Moreover the widening of the blood-vessels will 
certainly tend to further lower the pressure. It is probable that the 
nitrites do harm rather than good in these conditions. 

Its physiological action would indicate that it should be of service 
in all cases of spasm of the capillaries, of the bronchial tubes, and of 
the muscular system generally. 

Amyl nitrite is of very great value for the purpose of relaxing 
spasms; it will usually abort a paroxysm of asthma, but in practice 
it will be found that the asthmatic patient becomes so rapidly accus- 
tomed to the use of the drug as to make it of comparatively little value. 

Whenever for any reason it is desired to dilate the blood-vessels 
the nitrites are our most certain, in fact almost our only certain 
remedies. They are very largely used in cases of habitual high arterial 
pressure, especially in arterial fibrosis in which the increased peripheral 
resistance is developing, or has produced, increased cardiac power. 
In some cases of acute apoplexy with high arterial pressure they might 
be of great service. Oscar Berges and others have used amyl nitrite 
with good effect in migraine with capillary contraction. 

Administration. — The choice of the nitrites is governed almost 
solely by the quickness and duration of action desired. The effects 
of amyl nitrite come almost instantly and last from five to ten minutes. 
According to Korcynski the maximum effect from nitroglycerin ap- 
pears in from three to five minutes and disappears in about three 
quarters of an hour. Leech states that the effects of ethyl nitrite 
may endure for two hours. Sodium nitrite probably maintains its 
action for about the same length of time. Where it is desired to make 
a continuous impression on the system, the nitrite must be frequently 
repeated; the common custom of giving nitroglycerin three times a 
day is silly. 

Amyl nitrite is usually employed by inhalation, from one to three 
or five drops being placed on a handkerchief and held near the mouth 
or nose, the handkerchief being removed so soon as a sense of fulness 
of the head is experienced. We have given it by the mouth, dropped 
upon sugar and taken instantly in doses of two or three drops. 

Nitroglycerin may be given by the mouth in the form of the official 
solution, or it may be injected hypodermically. Sodium nitrite should 
always be dispensed in solution on account of its deliquescence. 
There is not at present sufficient evidence to enable us to decide as 
to the maximum amount of the drug which it is safe to give. In a 
case of cholera, D. B. Smith exhibited hypodermically two drachms 
in the course of an hour and thirty-six minutes without inducing any 
serious symptoms, and a dose of a dessertspoonful has been recovered 
from,* emetics being given. Doses of six to ten grains of sodium 

.4. J. Pharm., 1881, 137. 



170 GENERAL REMEDIES 

nitrite (G. A. Atkinson) in man sufficed to raise the pulse to 110 or 
120, with flushing of the face and intra-cranial throbbing; the symp- 
toms usually began in twenty minutes and lasted several hours, and 
were in no case disagreeably severe. 

Of the spirit of glyceryl nitrate a single drop is said to have caused 
insensibility, and in the case of Mr. Field, who took two drops, loss 
of consciousness and of the pulse at the wrist was complete. J. Noer 
attributed the following symptoms in a woman to the use of ten-drop 
doses of the alcoholic solution of nitroglycerin: The pulse was slow, 
intermittent, and very irregular, the pupils dilated, the urine scanty 
and containing considerable pigment. There were also pain in the 
region of the heart, intense headache, sense of constriction around the 
forehead, and great weakness of the muscles. 

Toxicology. — We know of no deaths recorded from amyl nitrite, 
though very alarming symptoms have resulted in various cases. Ten 
minims of a ten-per-cent. solution, hypodermically injected, are said 
to have been followed by two successive furious epileptic convulsions, 
each preceded by arrest of respiration and of the heart's action, to 
which arrest they were probably due.* Three drachms caused no 
other symptoms than violent vomiting. One drachm occasioned 
great weakness, cyanosis, and very feeble, slow, intermittent pulse. 
Two drachms caused vomiting within five minutes, great weakness 
of the pulse, slow respiration, temperature below 95° F., semi-coma, 
with hemoglobin, but no sugar or blood-corpuscles, in the urine for 
twelve hours after the poisoning. 

The best treatment for the poisoning would consist in favoring 
vomiting by apomorphine or other agents, and the use of artificial 
respiration and hypodermic injections of strychnine and digitalis. 

Eryihrol Tetranitrate. — A crystalline solid which, when pure, is colorless, but 
which is prone to decomposition and to become yellow. It is a violent explosive 
whose trituration has caused death. It is slightly soluble in water, but readily in 
alcohol. Its physiological action appears to be entirely parallel to that of glonoin, 
excepting in that its influence is less powerful and is much more prolonged. In man 
its effects are said not to be apparent in less than half an hour and to last for more 
than an hour. It has been especially recommended in the treatment of angina 
pectoris. As its alcoholic solution is explosive, it should always be used in tablets, 
whose preparation requires great care. Dose, from one-half to one grain (0.03- 
0.06 Gm.). 

LOBELIA. 

The leaves and tops of the Lobelia inflata, an herbaceous annual 
found throughout the eastern portion of the United States, producing 
pale or yellowish-green flowers in racemes. The dried plant has a 
slight irritating odor and a taste at first scarcely perceptible, after- 
wards burning, acrid, and attended by a flow of saliva. Proctor 
discovered the alkaloid lobeline, which was long believed to be 

* Strahan Uourn. Ment. Sci., xxx. 252), J. Roesen (Centralb. f. Klin. Med., 1888), George E. 
Shoemaker {Med. News, 1893, i.), and Stansfield (Brit. Med. Journ.). 



DEPRESSO-MOTORS 171 

liquid, until J. U. and G. G. Lloyd obtained it in broad, colorless, 
odorless, and tasteless crystals.* 

Official Preparations : 

Fluidextractum Lobelia 1 to 5 minims (0.0G-0.30 C.c). 

Tinctura Lobelia^ (as an emetic 1 fluidrachm, 

4 C.c.) 20 minims (1.3 C.c). 

Physiological Action. — Upon the lower animals lobelia produces, 
after a primary stage of motor-cord stimulation, progressive failure 
of motor power which is due to a paralyzing effect upon the peripheral 
endings of the motor nerve. According to Dreser when the nerves 
are protected from the action of lobelia there is evidence of a stimu- 
lation of the spinal cord. According to some observers there is pro- 
duced by a moderate dose, a primary excitation of the respiratory 
centre and also of the vomiting centre, which is followed by a paralysis 
of respiration. Its effects upon respiration are so much more powerful 
than upon the motor nerves that its action in mammals as a motor 
paralyzant is of little importance. Dreser also found that there was 
a palsy of the pneumogastric terminals in the bronchi. 

According to both Ott and Afanasieff, lobelia produces a rise of 
the arterial pressure which occurs after section of the cord. Ott 
believes that the effect is a direct one upon the muscles of the arterial 
walls; on the other hand, in the experiments of Afanasieff, lobeline 
caused in the frog's heart a period of increased work, followed, if 
the dose were large enough, by loss of power ending in diastolic arrest. 
In the later stages of lobeline-poisoning the arterial pressure falls 
progressively, so that it is probable that lobelia first stimulates and 
afterwards paralyzes both the heart and the arteries. A very impor- 
tant point to be noted is that the action of lobelia upon the circulation 
is entirely subordinate to its influence upon the nerve-centres, especially 
upon respiration, and is, therefore, of no value to the therapeutist. 

Therapeutics. — The former use of lobelia as an emetic, and for 
the purpose of relaxing spasm in various diseases, has been entirely 
superseded by more effective and less dangerous remedies. Lobelia 
remains, however, a valuable drug in the treatment of asthma, or 
acute bronchitis with bronchial spasm, in which it may be given in 
small repeated doses at long intervals, or in severe attacks every few 
minutes until nausea is induced. An infusion (one ounce to a pint) 
has been strongly recommended as a local application in the eczema 
produced by the Rhus toxicodendron, or "poison-vine." The dose of 
the tincture, as an expectorant, is twenty to forty minims (1.3-2.5 C.c); 
in the paroxysm of asthma, one-half to one fluidrachm (2-4 C.c.) 
every half-hour until nausea is induced. According to S. Nunes, 
from five to forty centigrammes of lobeline may be given a day, but 
in any case the first dose should not exceed one-fortieth of a grain, 
to be increased pro re nata. 

* The Messrs. Llovd also assert that there is a second alkaloid in lobelia, but the researches 
of Dreser render it probable that this second alkaloid is a derivative from lobeline. 



172 GENERAL REMEDIES 

Toxicology. — The symptoms produced by large doses of lobelia 
in man are nausea, soon followed by violent vomiting, accompanied 
by intense prostration, as is shown by feeble pulse, cold sweats, 
pale skin, and great muscular relaxation. Purging may or may not 
occur. Numerous cases of fatal poisoning by it have been recorded. 
The symptoms are those above mentioned, intensified; in some cases 
vomiting does not occur, and it is especially under these circumstances 
that fatal effects have been noted. Burning in the fauces and oesopha- 
gus, and epigastric distress, in addition to the intense prostration, 
bordering upon collapse and finally merging into complete col- 
lapse, with coma, stupor, muscular tremblings, and in some cases 
convulsions, precede the fatal termination. 

The treatment should consist in washing out the stomach with 
plenteous draughts of a warm solution of tannic acid, in the free 
exhibition of opium, alcohol, ammonia, strychnine, and digitalis 
and in the use of external stimulation by dry heat, frictions, mustard, 
etc., precisely as in poisoning from veratrum viride. 

GELSEMIUM. 

The rhizome and root of Gelsemium sempervirens, the yellow or 
Carolina jessamine, a beautiful climbing plant of the Atlantic Southern 
United States, distinguished by its large, axillary, very fragrant, 
clustered blossoms and perennial dark green leaves. According to 
Cushny gelsemium depends for its activity chiefly upon gelseminine; 
the alkaloid gelsemine which was discovered by Wormley being com- 
paratively feeble in its action. The very light, fibrous, dirty yellowish 
root has a bitterish taste. 

Official Preparations : 

Fluidextractum Gelsemii 3 to 5 minims (0.2-0.3 C.c). 

Tinctura Gelsemii (10 per cent.) 15 to 30 minims (1-2 C.c). 

Physiological Action. — Gelsemium produces in the lower animals 
symptoms similar to those which it causes in man, with the exception 
that convulsions are very generally developed. 

The convulsions are not always present, but they have been observed in the 
frog, pigeon, cat, rabbit, and dog. The loss of voluntary power precedes the con- 
vulsions, and in the careful experiments of Ringer and Murrell upon frogs it was 
found that the cord was rapidly exhausted by repeated irritations, so that convul- 
sions could not at once be induced. Bartholow states that in the rabbit, cat, and 
pigeon the convulsive movements are backward, sometimes amounting to complete 
somersaults. 

Nervous and Muscular Systems. — In large doses gelsemium causes 
increased reflex activity and even tetanic convulsions by its stimulat- 
ing effect upon the spinal cord. If the dose has been large enough this 
condition of motor excitement gives way to one of paralysis which is 
probably due to the effect both upon the spinal cord and the peripheral 
nerves. 



DEPRESSO-MOTORS L73 

The alkaloids gelsemine and gelseminine differ very markedly in their physio- 
logical effects. Gelsemine is primarily a stimulant to the motor cord (Ott and 
laylor') and in large doses a paralyzant to the peripheral ends of the motor nerves. 
According to Cnshny, the failure of Bartholow, of Ringer and Murrell, and other 
investigators to obtain evidence of the motor-nerve paralysis is due to the fact of 
their having used insufficient doses. 

Gelseminine on the other hand appears in no dose to act as a spinal stimulant, 
but causes in both the frog and the rabbit, according to Cushny, a gradually increas- 
ing paralysis by a depressant action upon the motor ganglia of the spinal cord. 
After very large doses this alkaloid also depresses the peripheral motor nerves. 

Respiration. — Gelsemium usually kills by a paralysis of respiration. 
According to the researches of Burdon Sanderson and of Ringer and 
Murrell, immediately after the ingestion the extent of the respiration, 
but not its rate, is increased; very shortly, however, both rate and 
depth enter a condition of progressive palsy ending in death. The 
respiratory changes are the product of a direct action upon the respira- 
tory centres, being uninfluenced by previous section of the vagi. 

Circulation. — The action of moderate doses of gelsemium upon the 
circulation is not pronounced, but the toxic dose depresses both the 
pulse-rate and the pressure. As this occurs after previous section of 
all the cardiac nerves and the spinal cord (Ott), it is probable that the 
poison exerts a direct influence upon the heart. How far or in what 
way it affects the arterial system we have no knowledge. 

Eye. — Ringer and Murrell affirm that decided non-toxic doses of 
the drug cause contraction of the pupil. However this may be, 
marked dilatation of the pupil is a very constant symptom in the 
poisoning, and the local application of gelsemine to the eye produces 
violent mydriasis, with paralysis of accommodation. 

It would seem probable that the mydriasis is due to an action upon the periph- 
eral nerve-endings in the eye. The palsy of the external rectus and the ptosis indi- 
cate that such action is paralytic, so that it is a probable conclusion that peripheral 
oculo-motor paralysis is the cause of the dilatation of the pupil. The falling of the 
jaw and the loss of the power of articulation indicate that all the motor nerves of 
the head are acted upon by the poison. 

Therapeutics. — Gelsemium was originally employed as an arterial 
sedative and febrifuge in the malarial fevers of the South, and subse- 
quently in other sthenic fevers. It appears in some way to depress the 
bodily temperature, but certainly possesses no controlling influence 
over the arterial system at all comparable to that of veratrum viride 
and aconite. Bartholow commends it .highly in pneumonia and 
pleuritis; its influence for good in these disorders would seem, however, 
to be chiefly associated with its power of lessening the rapidity of 
respiration and increasing the tendency to perspiration. It does not 
appear probable that any advantage to be derived from it will counter- 
balance the dangers attending its employment in the large doses 
required. In asthma, spasmodic laryngitis, whooping-cough, and 
nervous cough, in which it is also recommended by Bartholow, its 
employment seems more plausible, as in these cases there is a distinct 
spasmodic element. The testimony to its value in cases of trigeminal, 






174 GENERAL REMEDIES 

ovarian, and other neuralgias is strong. How it does good in these 
disorders is as obscure as is the nature of the neuralgias, and in our 
hands it has usually failed. The marked effect of the drug upon the 
facial nerves would appear to indicate its employment in facial neu- 
ralgias, and especially in facial spasmodic affections. In acute mania 
the drug may be employed in full doses as a calmative. 

Toxicology. — The earliest symptom of gelsemium-poisoning is a 
feeling of languor which is soon followed by dizziness and disturbance 
of vision, with, in some cases, a pain over the brows. Ringer and 
Murrell state that the pupil is contracted, but this is probably an 
inconstant result. Later the muscular weakness is extreme, and in 
several cases the flexors of the arms have been especially affected. 
The disturbance of sight is now very marked; double vision, or partial 
or even complete blindness, may exist; the pupil is widely dilated 
and immovable; the external rectus muscle is weakened, sometimes 
sufficiently to produce a marked internal squint; the eyelid droops, 
and is raised with difficulty or falls in paralytic ptosis. If the patient 
is able to walk at all, the gait is staggering; the jaw drops, articulation 
fails; the general sensibility is much impaired; the respiration slow 
and labored; the pulse feeble and thready; the skin bathed in a cold 
sweat; the bodily temperature greatly lowered. Sometimes drowsi- 
ness is felt after moderate doses of the poison, but consciousness may 
be preserved in the midst of very severe symptoms, although in all 
the fatal cases whose record we have met with it has been lost before 
death. The drug acts very promptly, symptoms usually appearing in 
about twenty minutes and beginning to subside in two or three hours. 
I. Ott has collected six cases of fatal poisoning, a teaspoonful of the 
fluidextract being the smallest amount that has caused death in the 
adult. Wormley believes that his chemical examinations have shown 
that in one fatal case the fluidextract ingested could not have 
contained more than one-sixth of a grain of the alkaloid. 

The treatment of gelsemium-poisoning should be conducted on 
general principles. Our present knowledge does not indicate that 
morphine and gelsemium are physiological antagonists, but George 
S. Courtright asserts that they have such relation, and details a case 
in which recovery occurred after the ingestion of from one to two 
teaspoonfuls of the tincture, one and one-half grains of morphine 
having been given hypodermically and one grain b}' the mouth. 

Tabacum. — Tobacco is no longer recognized by the United States Pharma- 
copoeia, and is not at present used in practical medicine. We shall here discuss it 
very summarily, referring the reader to the tenth edition of this treatise for a 
more elaborate study of its physiological action. 

Tobacco depends for its activity upon the presence of an alkaloid, nicotine, a 
poison of such intensity that it has caused death in three minutes. The fatal dose 
of nicotine has not been made out. One-thirty-second of a grain will cause serious 
symptoms; one-seventh of a grain has been recovered from. The symptoms pro- 
duced by tobacco in those unaccustomed to its use are horrible nausea and vomiting, 
giddiness, intense malaise, with weakness, followed, if the dose has been sufficient, 
by burning pain in the stomach, purging, free urination, extreme giddiness passing 



DEPRESSO-MOTORS 175 

into delirium, a rapid, running, and finally imperceptible pulse, cramps in the limbs, 
absolute loss of muscular strength, a cold, clammy skin, and finally complete 
collapse, terminating in death. 

In the lower animals, especially in the frog, to the symptoms commonly seen 
in man are added violent convulsions, which are of spinal origin and are followed 
after a time by paresis, which is probably also in part of spinal origin, although 
it has been demonstrated that tobacco is a powerful depressant to the motor or efferent 
nerves, acting primarily upon their peripheral filaments. The afferent or sensory 
nerves are much less affected than the motor, but are probably also depressed. 
The sympathetic ganglia are first stimulated and then depressed by nicotine. To 
these actions are probably due the increase of saliva and other secretions caused 
by small doses and the lessening of gland activity produced by large doses. Upon 
the voluntary muscles the drug has no action. 

Upon the circulation nicotine has a very distinct influence, producing first rise 
and afterwards fall of pressure. The rise of pressure is certainly in part due to 
stimulation of the cardiac muscles or ganglia, but probably is also in part the outcome 
of peripheral contraction of the vessels; and it is further probable that the final 
paralysis is due to a double depressing influence upon the heart and the arterial 
walls, although these points have not been distinctly proved. 

Upon the pupil nicotine acts as a myotic, probably paralyzing the peripheral 
ends of the sympathetic, and almost certainly stimulating the oculo-motor nerves. 

The only use now made of tobacco in medicine is in the preparation of ointments 
for painful hemorrhoids, and in the form of a strong wash for pruritus. Its free 
external use is always accompanied by danger, and has caused death. 

The dose of tobacco is five grains (0.3 Gm.), in infusion. 

Toxicology — A large number of deaths have resulted from the medicinal 
use of tobacco, Husemann stating that no less than ten fatal cases have been caused 
by tobacco enemata alone. Copland has seen a clyster containing half a drachm 
produce death. Even smoking has caused an acute fatal poisoning. Melsens affirms 
that the smoke of half an ounce of strong tobacco contains sufficient nicotine to 
prove fatal.* In the only case of criminal nicotine-poisoning on record, an unknown 
amount of the alkaloid was forced into the mouth of the victim, causing death in 
from three to five minutes. The treatment of tobacco-poisoning consists in wash- 
ing out the stomach, the free administration of ammonia and alcohol, the hypodermic 
use of moderate amounts of strychnine, and the employment of such external 
measures as dry heat, rubbings, etc. If these fail, artificial respiration should be 
maintained. The excessive use of tobacco produces in some persons serious nervous 
disturbance, such as insomnia, irritability, general feebleness; the most character- 
istic symptom is a peculiar irregularity of the heart's action, often accompanied 
by distinct intermissions. Amaurosis is also sometimes present.! Jonathan Hut- 
chinson affirms that he has seen this amaurosis recovered from under the use of 
opium and champagne without the abandonment of the habit of smoking. We 
have seen impotence as the only distinct symptom of chronic tobacco-poisoning. 

CONIUM. 

The U. S. Pharmacopoeia recognizes only the full-grown fruit, 
gathered while green, of Conium maculatum or Water Hemlock. 
The plant is umbelliferous, a native of Europe, but naturalized in 
the United States. The fruits are one to two lines long, roundish- 
ovate, striated, with five crenated ribs on the outer sides of the easily 

* For a number of cases, see Stilld's Therapeutics, ii. 374. 

t The diagnosis of tobacco amblyopia depends upon the history of the abuse of the drug, the 
failure to improve with optical therapeutics, and the presence of a scotoma, usually oval in shape 
and negative in character, particularly pronounced for red and green, while the periphery of the 
field of vision remains unaltered. If, in addition, there is a quadrant-shaped patch of atrophic 
pallor in the nerve-head, the diagnosis becomes still more certain. Atrophy of the nerve may result, 
but in many cases there is no structural change, as the symptoms may go off in a few hours (De 
Schweinitz's Toxic Amblyopia). 



176 CJENERAL REMEDIES 

separable halves, and have a peculiar mouse-like odor. Conium is 
famous in history as the penal poison of the Greeks, with which 
Socrates was killed. The active principle is coniine, a yellowish, oily, 
liquid alkaloid, highly volatile, of a strong odor similar to that of 
the urine of mice, and of a very acrid taste. It is freely soluble in 
alcohol and in ether, and slightly so in water, with which it forms a 
hydrate, and it coagulates albumin; when exposed to the air it under- 
goes decomposition, becoming first brown, afterwards resinous; heat 
accelerates the change. The U. S. Pharmacopoeia directs that 0.5 
per cent, of the alkaloid shall be present in the drug. 

Preparation : 

Fluidextractum Conii 1 to 3 minims (0.06-0.18 C.c). 

The extract was formerly official but is no longer recognized, the dose of it was 
| to 1 grain (0.03-0.06 Gm.). Coniine Hydrobromide is occasionally employed 
in doses of ^ to T 'i grain (0.003 to 0.005 Gin.). 

Local Action. — Upon the mucous membranes conium acts as an 
intense irritant. In a concentrated form it is probably fatal to all 
highly organized tissues, Christison having proved this to be true in 
regard to the muscles which are not influenced by the alkaloid taken 
internally. 

Elimination.— It is absorbed with great rapidity, and escapes 
through the system chiefly if not solely through the kidneys. Zaleski 
and Dragendorff have found it abundant in the urine during the first 
twelve hours of the poisoning; Prevost has seen the urine of poisoned 
animals cause in a frog the characteristic general palsy, and in a 
doubtful case of poisoning this physiological test might decide the 
diagnosis. 

Nervous System. — The retention of consciousness and all the 
mental faculties almost up to death in conium-poisoning shows that 
the drug has but little influence upon the general cerebral cortex. 
According to Lautenbach, the convulsions which occur in the lower 
animals are, however, of cerebral origin, since after division of the 
cord they were confined to those portions of the body situated above 
the section. They are probably asphyxial or of other secondary 
character. 

The characteristic effect of conium is an ever increasing muscular 
weakness. This is due chiefly to a paralysis of the peripheral endings 
of the motor nerves although there is evidence that the spinal cord 
is also affected. The drug seems to exercise a similar paralytic in- 
fluence on the sensory nerve-endings but much less powerfully. In 
mammals respiratory failure, probably due to palsy of the phrenic 
nerve, usually leads to the death of the animal before the other 
motor nerves are completely insensible to electrical stimulation. 

The original discovery of Kolliker, that the paralysis of coniine-poisoning is due 
to paralysis of the efferent or motor nerves, has since been abundantly confirmed. 

Kolliker demonstrated that in the poisoned frog immediately after death the 
galvanic current applied to the nerve is powerless to induce contractions; that if by 
tying the aorta access of the poison be cut off from the hind legs, there is a stage of 



DEPRESSO-MOTORS 177 

the poisoning in which galvanic stimulation i>f the nerve of the front, leg fails (,o 
affect the tributary muscles, although it does produce reflex contractions in the hind 
legs; proof that the anterior afferent nerves and the spinal cord still retain func- 
tional activity after this activity has been lost in efferent nerves reached by the 
poison. These experimental results have been confirmed by Funke, bv Guttmann, 
and by lVlvette and Martin-Dainonrette. These last-named observers also noted 
thai when coniine and strychnine were given simultaneously to a frog from one of 
whose sciatic nerves the circulation (i.e., direct access of the poison) was cut off 
in cither of the manners spoken of, they produced by their conjoint action a com- 
mingling of paralysis in all other parts of the body with violent tetanic spasms in the 
protected leg, — a commingling explainable only on the supposition that the coniine 
paralyzed all the motor nerves to which it. had access through the circulation. These 
experiments upon the frog have been confirmed by B. F. Lautenbach, Verigo, A. 
W. Hofmann, Prevost, H. Schultz, and Fliess. Hayashi and Muto have shown that, 
although the nerves of purely voluntary motion are acted upon in the mammal 
by coniine, the phrenic nerve, at least in the rabbit, is even more susceptible to its 
influence. 

It has been generally believed that coniine does not affect the sensory nerves, 
but the evidence appears to show that this is not correct; only that the action upon 
the sensory nerves is so much less decided than that upon the motor fibres that it 
counts very little in the general influence of the drug. 

In 1875 Gubler called attention to the local influence of conium in benumbing 
the cutaneous sensibility, and Lautenbach found that when he tied the abdominal 
aorta and left axillary artery in the frog, and then injected a dose of coniine into 
the abdomen, irritation of the leg whose nerve was not protected from the poison 
failed to cause reflex movements at a time when irritation of the protected nerves 
produced reflex actions in distant parts of the body. 

The exact influence of coniine upon the spinal cord cannot yet be considered 
absolutely determined, but it is most probable that the poison has a feeble 
depressant action. Verigo asserts that it is a powerful spinal depressant, and 
Pelvette and Martin-Damourette say that it acts as an excitant. Lautenbach, 
in carefully investigating the subject, failed to obtain, under any circum- 
stances, evidences of excitement of the cord; he did succeed in producing loss of 
reflex activity when the nerve was protected by tying the artery in the limb, but, 
as in all but two of fifty-two experiments the reflexes in the protected limb were 
not greatly reduced until just before death, it is plain that any action upon the 
spinal cord is unimportant and dominated by the more powerful peripheral influences 
of the poison. 

Muscles. — All observers agree that in conium-poisoning the 
muscles themselves are not affected. 

Pupil. — The pupil is generally dilated by coniine; but both Von 
Praag and Verigo assert that the phenomenon is not constant, at least 
in animals. The ptosis of conium-poisoning indicates that the dilata- 
tion of the pupil is due to oculo-motor paralysis. The known action 
of the drug upon nerve-trunks indicates that this paralysis is periph- 
eral, — a conclusion corroborated by the experiments of I. Hoppe 
and of Lautenbach, each of whom found that when coniine is 
dropped into the eye of an animal it causes at first contraction, 
apparently due to the intense irritation, and afterwards dilatation, 
of the pupil. 

Temperature. — Verigo, Von Praag, and others affirm that lethal 
doses of conium cause a decided lowering of temperature; but Lauten- 
bach asserts that the drug decidedly increases the temperature both 
when in therapeutic and when in toxic doses. 
12 



178 (iENERAL REMEDIES 

Circulation. — No sufficient investigation has as yet been made upon 
the action of coniine upon the circulation. Lautenbach states that 
the arterial pressure falls immediately after the injection of coniine, 
and afterwards rises far above the normal point, and that the pulse is 
at first accelerated, but afterwards retarded. The secondary rise of 
pressure is probably due to asphyxia. The primary pulse-acceleration 
is explained by the observation of Pelenard (confirmed by Prevost) 
that the pneumogastrics are paralyzed before the motor nerves. 
Prevost finds that the heart itself is scarcely affected by the poison. 

SUMMARY. — The chief symptom of poisoning' by conium is a 
failure of voluntary and involuntary movement, the result of a pro- 
gressive paralysis of the motor nerves. The cerebrum is not affected, 
hence consciousness is preserved to the last. The pupil is dilated 
by a peripheral paralysis of the oculo-motor nerve. The sensory 
nerves and the spinal cord are probably feebly depressed. It is 
probable that the alkaloid does not directly act upon the circulatory 
apparatus except to paralyze the pneumogastrics. 

Therapeutics. — The paralytic action of conium naturally suggests 
its use in spasmodic affections; and accordingly it has been tried in 
chorea, in paralysis agitans, in whooping-cough, and in other diseases 
of similar nature. As the depressant influence of conium is chiefly 
upon the motor nerve, and as the phrenic nerve seems more sensitive 
to its effect than other motor nerves, it is evident that the drug is very 
limited in its power for good. In maniacal and hysterical excitement, 
the drug in full doses is said to produce a highly favorable condition 
of calm and relaxation; and in the treatment of the insane, conium 
is much used by some alienists. 

Conium was formerly employed to relieve pain or as a deobstruent 
and alterative in chronic glandular or arthritic diseases, and even in 
cancer, but for these purposes has passed entirely out of vogue. The 
belief that it possesses alterative qualities does not seem to be well 
founded. 

Toxicology. — Full physiological doses of conium produce in man 
quietude, languor, and muscular weakness. After toxic doses the 
weakness becomes extreme, forcing the patient to the horizontal 
position, or causing him to stagger or fall from weakness of the legs 
when he attempts to walk. This weakness has in some cases been 
attended by burning in the mouth, fauces, or stomach, nausea, vomit- 
ing, and with a sense of pressure or even with severe frontal pain. 
As the case progresses the paralytic symptoms become everywhere 
pronounced. The pupils sooner or later dilate;* amblyopia from 
paralysis of accommodation, diplopia from irregular weakness of the 
ocular muscles, and ptosis are almost universally present, and the 
voice may be weakened to a whisper or lost. Sensibility is main- 
tained to the end. Free salivation or free sweating sometimes occurs. 

* The experiments of Poehlmann (quoted by Husemann) show that very grave symptoms 
may be induced and yet the pupils remain natural; but sooner or later they probably always dilate. 



DEPRESSO-MOTOKS 179 

The circulatory phenomena are very subordinate; though the 
pulse-rate may at fust fall, later it becomes more rapid. Consciousness 
is usually preserved until the last, but may be lost in asphyxial coma 
Borne minutes before death, which results from paralysis of respiration. 

After death from conium no distinctive lesions are to be found, 
only the usual indications of death from asphyxia. The treatment 
consists in the immediate evacuation of the stomach and the exhibi- 
tion of tannic acid,— the t annate formed is, however, probably more 
or less poisonous, — with the use of external heat and of internal 
stimulants: artificial respiration should steadily be maintained so long 
as there is the faintest indication of cardiac action. No physiological 
antidote is known; but strychnine and other respiratory stimulants 
should be used. 

We have met with accounts of but four fatal cases of such character.* In one, 
; hai of the mistress of Dr. Hermann Jahn, from ten to fifteen drops of the alkaloid 
killed in a few minutes (quoted by Husemann). 

In another case a medical electrician, suffering from blepharo-facial spasm, be- 
ginning four hours after the last of a previous series of divided doses of a fluid- 
extract amounting to one hundred and eighty drops, took at 4.10, 4.40, and 5.15 
p.m. fifty minims (one hundred and fifty in all) of "Squibb's fluidextract. " At 
6.10 there were nausea, intense muscular weakness, partial ptosis, diplopia, and 
great difficulty of speech; the pulse was 60. Shortly after this the man became 
unable to speak or to swallow. He made signs for electricity, and, on being asked 
whether the chemical or the faradic current, indicated the latter, and also the place 
of application of the electrodes, but was unable to hold one of the latter. Shortly 
after this, on being raised up, he dropped dead. A fourth case, in which a child 
five years old died of asphyxia preceded by coma and paralysis as the result of 
taking a drachm of chloroform-water containing five grains of the extract of conium, 
is recorded. f 

Aspidosperma. — Quebracho. — Aspidosperma is the bark of an evergreen South 
American tree, Aspidosperma Quebracho-bianco. It contains at least six alka- 
loids, aspidospermine, aspidospermatine, aspidosamine, quebrachine, hypoquebrachine, 
and quebrachamine. The aspidospermine of commerce (amorphous aspidospermine) 
is not a pure principle, but probably contains all the alkaloids of the bark. Accord- 
ing to Merck & Co., it consists principally of aspidosamine. 

Physiological Action. — The general physiological action of aspidosperma 
has not been carefully enough studied to permit definite conclusions concerning its 
effects. It would seem that the various alkaloids have entirely different effects 
upon the system and in some respects are even antagonistic; thus, Schiffer has found 
that the extract of quebracho-bianco causes in the rabbit general muscular weakness 
with greatly diminished reflexes and increased frequency in breathing. Eloy and 
Huchard found that aspidospermine, quebrachine, and hypoquebrachine produced 
violent convulsions, which were followed, when the dose was large, by paralysis. 
According to Penzoldt, aspidospermine produces complete motor paralysis in the 
frog, with slowing of the pulse. 

Respiration. — Penzoldt was the first to describe the marked action of que- 
bracho upon the respiration. He described the effect produced in a dog as dyspnoea. 
In an elaborate research by Wood, Jr., and Hoyt on the effects of the commercial 
aspidospermine, it was shown that this substance produces a marked increase in 
both rate and depth of the respiration, the amount of air moved being augmented 

* See Edinburgh Med. and Surg. Jqurn., 1845; Sanitarian, June, 1875; P. J. and Tr., xvi. 102. 
t According to H. Hayashi and K. Muto, the mimimum fatal dose of coniine for rabbits 
intravenously given, is between fifteen and twenty milligrammes. 



180 GENERAL REMEDIES 

in some cases four hundred per cent. Secondary depressions was produced only by 
doses large enough to kill, and in these cases the stage of diminished respiratory 
activity was very short. 

H. C. Wood, Jr., has since found (research not yet published) intense conges- 
tion and ecchymoses in the lungs following the intravenous injection of quebrachine. 

Blood. — Penzoldt noted that the blood in the veins as well as in the arteries 
after the administration of aspidosperma had a bright red hue, and attributed the 
increase in the respiration to a dyspnoea brought about through the inability of the 
corpuscles to give up their oxygen. Wood, Jr., and Hoyt, however, believe that 
the change in the blood is the effect rather than the cause of the increased breathing. 
They were unable to find any spectroscopic change in the blood, either in the poi- 
soned animal or when the aspidospermine was added to the blood outside of the 
body; they were unable to note any diminution of the oxidation power of the aspi- 
dospermine blood towards guaiac, and finally they noted that if the animal was 
asphyxiated the blood assumed the venous hue all over the body. 

Circulation. — According to Wood and Hoyt,, commercial aspidospermine pro- 
duces a marked temporary fall of the blood-pressure, wliich was permanent if the 
dose had been large. During the period of low blood-pressure, it was found that 
irritation of the central end of the vagus produced a rise of pressure, showing that 
the vaso-motor system was not paralyzed. As the pulse was not slowed, it would 
seem probable that aspidospermine lowers the blood-pressure by a depressant action 
on the cardiac muscle. 

Temperature. — Penzoldt found that, although quebracho had but little effect on 
the temperature of the normal animal, in a dog with septic fever it caused marked 
diminution in the temperature. In clinical experiments, however, it did not seem to 
exercise such effect in human fevers. 

Therapeutics. — Aspidosperma has been used with asserted good results in 
various forms of respiratory embarrassment, as asthma, emphysema, and bronchitis. 
It is even stated that it will relieve uremic and cardiac dyspneea. 

The commercial amorphous aspidospermine may be given as representing prob- 
ably the whole effects of the drug, in doses of from one-eighth to one-half grain 
(0.008-0.03 Gm.); the dose of the fluidextract is a quarter to one fluidrachm (l^t 
C.c.); of the solid extract, one to three grains (0.06-0.2 Gm.). 



HYDROBROMIC ACID. 



REFERENCES. 

PHYSOST1GMA. Subbotin A. K. M., 1869, v. 285. 

t i tu ,o-,- Tachau A. Hk., 1865, 70. 

Amagat . . . . J. de Th„ 18.0. yi . E ancl Leven . C . R. S. B., 1805, 161. 

Aenstein and busTSCHiNSKY U. P. L. \\., \intschgau W. A. W., 1807, lv. Abt. 

Theil n. 80. jj 49 

BouBNEViLLh- Revue Photog. d. Hopitaux, Westebmann .. . .S. Jb., exxxviii. 290. 

P'ngelhardt U. P. L. W., ii. 520. 

Fraser Tr. R. S. Ed., 1870, xxiv. 

Grunhagen V. A. P. A., xxx. 521. Albertoni A. E. P. P., xv. 250. 

Harnack and Witkowski. . A. E. P. P., v. and Amory Physiol, and Therap. Action 

x. 301. of Bromide of Potassium, 

Hiller Charittf Annalen, 1883, 235. Boston, 1872. 

Husemann A. E. P. P., 1878, ix. 434. Amory B. M. S. J., Oct. 1808. 

Keyworth Gl. M. J., 1809, n. s., i. 54. Bard P. M. T., June, 1871. 

Lasckewich Y.A. P. A., 1800, xxxv. 294. Bartholow Bromides. Providence, 1871. 

Leibholz Vierteljahrsch. f. Gerichtl. Bernard The Clinic, Sept. 1874. 

Med., Berlin, 1892. Bill A. J. M. S.. July, 1808. 

Leven and Laborde. S. Jb., cxlvi. 130. Chittenden and Culbert. .S. L. C. Y. 

Lodderstaedt . . . B. K. W., 1888. Crisafdlli G. I. M. P., 1899. 

Merson Journ. Ment. Science, Jan. Damourette and Pelvette. .B. G. T., 1807, 

1875. lxxiii. 249. 

Ogiu Ther. Geg., 1904. Dougall Gl. M. J., Feb. 1893. 

Pal Cb. P., 1900-01, xiv. Do yon and Cazeneuve. .Lyon M., 1889, lx. 

Papi S. Jb., cxlii. 287. Eigner Wien. Med. Pres.se, 1880, 

Roemer St. L. M. S. J., 1873, 307. No. 25. 

Rosenthal A. Ph., 1803. Eulenberg and Guttmann. . V. A. P. A., 1867, 

Rossbach and Frohlich. .Pharmakol. Unter- xli. 

such., i. 50. Fere and Herbert. .C. R. S. B., 1891, iii. 

Schmiedeberg . . .Grundriss d. Arzneimittel- Gillespie A. J. M. S., Oct. 1870. 

lehre, Leipzig, 1895, 109. Guttmann V. A. P. A., lxxiv. 

Sohultz A. P., 1898. Hondo B. K. W., 1902, xxxix. 

Scuweder In. Dis., Dorpat 1889. Huette C. It. S. B., 1850. 



DEPRESSO-MOTORS 



181 



REFERENCES (Continued). 



Larorde A. de P., 1888, i. 428. 

l.i »i,kv V. A. P. A.. L869, xlv. 191. 

Namias.. . ,C. K. S. B., boc. 282. 

I'liisKK D.J. M. 8., 1869, xlvii. 324. 

Ql in, ki \. I'll., 1868, \\\v. 158. 

Ilimrnr G&l. llclulom, 1S69. 

Ki u in ui' B. M. S. J„ civ. 505. 

liiN.in: and Morbhead J. \. I'., xii. 71. 

S UBBON 3. Jb., cxliii., 17. 

SCHODTEN A. Ilk., 1871, xii. 97. 

SCHULI Z. B., 1883, xix. 801. 

MONOBROMATED CAMPHOR. 

Bourneyii.i.e .... Prog. M„ 1S74. 

DbNEFFB Presse M. B., 1871. 

I. iwaON Practitioner, 1874, 1875. 

Pathaui/t Brotnure ile Camphor, Paris, 

1875. 

Peixicani S. ,1b., ci. 

Peters S. .lb., ci. 126. 

Rosenthal S. Jb., ci. 127. 

BROMALIN. 

Kollartis S. Jb., Bit. eclxxvii. 

NITRITES. 

Aldridge West Riding Lunatic Rep., 

i. 187. 

A.mez-Droz A. de P., Sept. 1873, 467 

Atkinson J. A. P., 1888, xxii. 

Berger Allg. Med. Central-Zeitung, 

May, 1871. 

Bock A. E. P. P., 1898, xii. 

Brcnton and Tait. .St. Barthol. Hosp. Rep., 

xxii. 140. 

Field B. M. J., 1880, i. 406. 

Fii.ehne A. G. P., ix. 478. 

Foster B. M. J., 1874, i. 77. 

Gamgee Philos. Trans., 1808, 589. 

Gaspy V. A. P. A., lxxv. 310. 

Gray Gl. M. J., 1871, 188. 

Haldane, MAKc.iLLand Mavrogordata. J. P., 

1897, xxi. 

Hare B. M. S. J., Nov. 1884. 

Hay Pract., xxx. 422. 

Henocql-e C. R. S. B., 1883, v. 609. 

Hoffmann A. P., 1872, 747. 

Hoppe-Seyler .. .Z. P. C, ii. and iii. 54. 

Jenks P. M. T., 1872, ii. 404. 

Korczynski S. Jb., exciii. 132. 

Leech L. L., 1893, i. 

Leech Med. Chron., 1869, ix. 

Manassein and Sassezki. .St. Petersburg Med. 

Wschr., 1879, iv. 392. 

Marshall J. P., 1897, xxii. 

Mayer and Friedrich. .A. E. P. P., v. 63. 

Mitchell P. M. T., v. 553. 

Noer T. G., 1887, 459. 

Pick C. M. W., 1873, No. 55. 

Reichert N. Y. M. J., Jul v. 1881; A. J. 

M. S., lxxx. 180. 



Richardson, 

R.OHRMANN. . 

Sciiri.i.Klt. . . 

Smith 

Wood 



Afanasikif. 
Dreser 

N U N ES 

Ott 



.Brit, and For. Med. Cliir. 

Rev., July, 1867. 
,Z. P. G, v. 233. 
.B. K. W., 1874, No. 25. 
, ,L. M. R., Oct. 1873. 
.A. J. M.S., July, 1871. 

LOBELIA. 

. ,L. M. R., Aug. 16, 1886. 
..A. E. P. P., 1889, xxxvi. 

. .S. Jb., cexxix. 
. .B. M. S. J., 1875; P. M. T„ 
vi. 



OELSEM1UM. 

Bartholow .. .Pract., v. 202. 

Courtrkiht Cincinnati Lancet and Ob- 
server, 1876, 693. 

Gushing A. E. P. P., xxxi. 49. 

Ott P. M. T., v. 691; vii. 289. 

Ringer and Murrell. .L. 1^., 1875, ii. 908; 
1876, i. 83. 

Taylor Richmond and Louisville 

Med. Journ., 1875, 606. 

TOBACCO. 

Copland Diet, of Pract. Med., art. 

Colic. 

Husemann Handb. d. Toxicol., ii. 483. 

Hutchinson M. T. G., 1884, i. 40. 

An. d'H., 1861, ii. 

CONIUM. 

Fliess A. Ph., 1882, 111. 

Funke Sb. G. W., Leipzig, 1859, 

xi. 23. 

Gobler B. G. T., 1875. 

Guttmann B. K. W., 1868. 

Hayashi and Muto. .A. E. P. P., xlviii. 
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Leipzig, 1855, i. 

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Phila., 1875. 

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31. 

ASPIDOSPERMA. 

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1880, xvii. 565. 

Schiffer A. Ph., 1883, 249. 

Woon, Jr., and Hoyt. .U. P. M. B., Sept. 1903. 



ORDER II.— CARDIANTS. 



FAMILY I.— CARDIAC STIMULANTS. 

The term cardiac stimulants is here used to designate a number 
of medicines which, when given internally, increase the power and 
force of the circulation, and are used by the physician for such pur- 
poses. There are some substances which are heart-stimulants in 
reality, but which possess other properties in so great a degree as to 
overshadow their cardiac relations, and are therefore not used by the 
physician to affect the circulation. Such medicines are considered 
in connection with those powers which give them their clinical value, 
and are not included in the present class. Some of the members of 
the present class are slow in their operation, some rapid. Some 
produce increase in the pulse-rate, some lower it. It is evident, then, 
that no general indications can be laid down for their use, but that 
medicines so diverse must be studied individually. 

AMMONIUM. 

Ammonia is a colorless, irrespirable, highly irritant gas, of a strong 
alkaline reaction, extremely soluble in water. It is obtained upon a 
large scale as a waste product in the manufacture of coal-gas, and is 
official in watery and alcoholic solutions and in various salts. 

When ammonia gas is dissolved in water it unites, according to 
the generally accepted theory, with the elements of water to form the 
hydroxide of a base, ammonium, similar in its chemical properties 
to sodium and potassium. Thus NH 3 + H 2 = NH 4 OH. 

This base ammonium possesses marked physiological properties, 
and eight of its salts are official. In many of these salts, however, 
the acid radical is so much more important than the basic that they 
are considered in the articles on their acid constituents. In this article 
is considered only the action of the ammonium base and those salts 
in which the acid radical is of little importance. 

Ammonium hydroxide is known only in the form of its solution. 
This is colorless, with the characteristic pungent odor of ammonia and 
an alkaline taste. The concentrated solution is actively caustic. 

Ammonium carbonate of the U. S. Pharmacopoeia is a mixture of 
the acid ammonium carbonate and ammonium carbamate and 
should yield 31.58 per cent, of gaseous ammonia. It has an alkaline 
reaction and the characteristic odor and taste of ammonia. It 
occurs in white, translucent, fibrous masses, which on exposure 
182 



CARDIAC STIMULANTS 183 

become opaque and efflorescent, parting with both ammonia and 
carbonic acid. It is soluble in four and a half times its weight of water. 
Ammonium chloride or Sal Ammoniac, when pure, is a white 
crystalline powder freely soluble in water, without odor, but having a 
puugenl salty taste. It is neutral or slightly acid to litmus. 

Official Preparations : 

Aqiui Ammonia; l'ortior (28 per cent.) Not used internally. 

Aqua Ammonite (10 per cent.) 15 to 45 mini ms (1-3 C.c.). 

Spirit us Ammonia; (10 per cent.) 15 to 45 minims (1-3 C.c). 

Spirit us Ammonia; Aromaticus 15 to 45 minims (1-3 C.c). 

Ammonii Carbonas 5 to 10 grains (0.3-0.6 Gm.). 

Ammonii Chloridum [Sal Ammoniac] 5 to 10 grains (0.3-0.6 Gm.). 

Liniment urn Ammonia; (35 per cent.) External use. 

Local Action and Elimination. — In solution, ammonia is a very 
powerful irritant and even escharotic, producing, if kept in contact 
with the skin, blistering, and finally sloughing, and causing the most 
serious disturbances of mucous membranes which it reaches. This 
local action is sufficient to interfere with its absorption, and it is 
difficult to produce distinct constitutional symptoms with it in man. 
Its volatility and the extreme fugaciousness of its action would seem 
to indicate its elimination by the lungs; but Feltz and Ritter were 
not able to find it in the breath of poisoned animals, and Magnus has 
apparently demonstrated that it will not pass through the alveolar 
walls. Bence Jones believed that ammonia is oxidized in the system 
because he found that its administration increases the acidity of the 
urine and also the amount of nitric acid. The theory that some por- 
tion of the ammonium is, in conjunction with carbonic acid, con- 
verted into urea is held by many physiologists.* The neutral salts 
of ammonium are mostly eliminated unchanged (see Rabuteau). 

Physiological Action. — When ammonium hydroxide is injected 
into the veins of animals in considerable quantities, it causes violent 
convulsions, with remarkable disturbances of the respiration, fol- 
lowed, if the dose has been large enough, by death in a very short 
time. Billroth states that the temperature falls enormously in 
animals poisoned with ammonia. 

Cerebrum and Spinal Cord. — Ammonium has no effect upon the 
cerebrum. The tetanus produced by it in the lower animals is accom- 
panied by great increase of the reflex activity (Funke), and is cer- 
tainly of spinal origin, since it occurs below a section of the spinal 
cord (Lange, Formanek) and is not prevented by tying the artery 
of a limb (Funke). It would therefore appear that the toxic dose of 
ammonium is a powerful stimulant to the motor spinal cord. Upon 
the sensory cord it seems to have little or no action. 

Respiration. — The intravenous injection of ammonia causes in the 
animal a great acceleration of the breathing, which after large doses 

* This theory is of such purely physiological interest that it is dismissed with the following 
key to the literature: Arch. f. Exper. Path. u. Pharm., ii., viii., x. 125, xii. 77; Zeitschr. /. Physiolog. 
Ctiem., ii. 29, iv. 36; Zeitschr. f. Biol., xiv. 



J 



184 GENERAL REMEDIES 

may be preceded by temporary arrest of respiration in expiration. 
The cause of this arrest is uncertain, Funke observing it after section 
of the vagi, while in the experiments of Lange it was always absent. 
Section of the vagi, however, does not interfere with the increased 
rapidity of the breathing, the change from the deep breathing of 
divided vagi to the extremely rapid respiration of ammonia-poisoning 
being colossal (Funke). Further, Binz has found that the increase 
of the respiratory rate in chloralized rabbits is accompanied by 
a great increase in the amount of air breathed. Ammonium is, 
therefore, a powerful direct stimulant to the respiratory centres. 

Circulation. — The intravenous injection of ammonium hydroxide 
both in normal and curarized animals produces an immediate fall 
in the blood-pressure, followed by a very decided rise if the dose has 
not been too large. If, on the other hand, an overwhelming amount 
of ammonium or one of its salts is employed, the fall of blood-pressure 
continues until the arrest of the heart in diastole. When the dose 
has been sufficient, this cardiac arrest is immediate. In the experi- 
ments of Lange and of Formanek, the primary fall of blood-pressure 
occurred after section of the spinal cord, also after ligation of the aorta; 
without doubt it is due to the direct action of the concentrated drug 
upon the heart. The rise of pressure which is the characteristic effect 
of the moderate dose of ammonium must be due to a stimulating action 
upon the heart or upon the peripheral vessels, since, according to 
both Lange and Formanek, it occurs after previous section of the cord. 
The experiments of Formanek, in which it was shown that if the 
thoracic aorta were temporarily ligated, ammonium still distinctly 
elevated the blood-pressure, demonstrate that the drug acts upon the 
heart directly, but it is probable that the muscle-fibres of the arterioles 
are also affected; so that the conclusion must be reached that ammo- 
nium is a primary stimulant both to the heart and to the muscle- 
fibres of the arterioles, although when in overdose it is a paralyzant 
to both heart and arterioles. 

In regard to the action of ammonium upon the pulse-rate, the 
evidence is somewhat discordant. All observers seem to be in accord 
that the pulse is for a time increased in rate, which increase in rate, 
according to Lange, does not occur after section of the spinal cord, 
and according to Formanek, is prevented by extirpation of the stellate 
ganglion of the sympathetic. The increased rate appears, therefore, 
to be due to a stimulating influence upon the cardiac accelerators. 
Formanek has found that at the time of the highest pressure there is 
marked slowing of the pulse, which is prevented by section of the vagi, 
and which he concludes, therefore, to be due to stimulated inhibition.* 

According to F. W. Bocker the long use of ammonium chloride 
is accompanied by a decided decrease in the solids of the blood, — 
an observation confirmed by Arnold. 

* Formanek believes that the vagi are directly stimulated, but his tabulated experiments 
seem to show that the reduction of the pulse-rate is inconstant, and it is possible that it is a 
secondary result due to high blood-pressure. 



CARDIAC STIMULANTS is.'. 

According to Feltz and Ritter, the blood of a dog killed by ammonia 
is incapable of absorbing oxygen, and contains much less than the 
normal amount of gas, while the red disks resist the action of acetic 
acid to a markedly abnormal degree. 

Therapeutics. — Externally, ammonium hydroxide is much used as 
a constituent of irritating liniments, and, on account of its efficiency and 
cheapness, is very valuable. By inverting a watch-glass full of the 
stronger water of ammonia upon the skin, a blister may be raised 
in a very few minutes; but, as the effects of the application are 
apt to be severe, the use of it is justifiable only under rare 
circumstances. 

Internally, ammonium is largely used for the relief of acute heart 
failure, as in shock and collapse. It must be remembered, however, 
that the drug is not well absorbed through the gastric mucous mem- 
brane and if used, therefore, as a circulatory stimulant, it should be 
administered hypodermically; or better, intravenously. In failure 
of the heart from anesthetics* or other poisons, animal or vegetable, 
in sudden collapse in disease, as is sometimes seen in the exanthemata, 
in cholera, and not rarely in pernicious malarial fever f or after surgical 
operations or injuries, hypodermic injections of ammonia have seemed 
to be in a number of reported cases of very great service. The effects 
seen in fainting by holding various forms of ammonium below the 
nostrils, usually in the form of smelling salts, is due to a reflex stimu- 
lation the result of irritation of the nasal mucous membrane. The 
ammonium being an irrespirable gas it is evident that sufficient of 
it cannot be absorbed to exercise any direct action upon the circula- 
tion. Moreover, similar results may be obtained by tickling the nose 
with a feather. When the failure of the circulation depends upon a 
slow and persistent cause, as in adynamic fevers, ammonia is not 
generally useful, but may be employed as an adjuvant to alcohol in 
the crisis of the disorder. As a stimulant, ammonia may be useful in 
poisoning by venomous serpents, but the statements that have been 
made that it is antidotal to venom have no foundation. (For detailed 
discussion, see the tenth edition of this treatise.) 

Ammonia appears to have a tendency to act upon the mucous 
membrane of the lungs, and its salts, especially the carbonate and 
the chloride, are used as stimulant expectorants in acute bronchitis 
when free secretion has just been established. In chronic bronchitis 
it may be administered from time to time when the secretion is not 
very free. 

Although there is sufficient reason for believing that ammonium 
chloride especially affects the respiratory mucous membrane, the 
statement of Bocker, that it hastens very greatly the nutritive changes 
and the exfoliation of the epithelium in all mucous membranes, is 
in accord with clinical experience as to its value in various gastro- 

* Kinger (Practitioner, xxvii.) finds that ammonia added to the frog's heart depressed with 
chloroform, iodoform, etc., has a pronounced effect in re-establishing its action, 
t See Zuelzer (Revue de Therap. Med.-Chir., July 1, 1872). 



186 GENERAL REMEDIES 

intestinal conditions. In Germany more than in this country it has 
been extensively used in the treatment of chronic gastric and intestinal 
catarrhs. The statement of W. Stewart, made in 1870, that it is an 
effective remedy in chronic torpor of the liver and chronic hepatitis, 
has been sustained by subsequent clinical experience, and it has 
become a standard remedy in these affections and in catarrhal jaundice. 
The dose in hepatic diseases is twenty to thirty grains (1.3-2 Gm.) 
in four or five ounces of water, three or four times a day, administered 
when the stomach is empty. As a stimulant antacid, it is frequently 
of service in cases of headache from gastric acidity. (See p. 632.) 

Toxicology. — Ingested in large amount, ammonia acts as a violent 
corrosive poison, the symptoms of its constitutional action being 
entirely lost in those caused by its local influence. Violent pain in the 
mouth and fauces, in some cases intense burning in the larynx with 
sense of choking and great difficulty of breathing and rapid asphyxia; 
more commonly violent abdominal pain, vomiting, bloody purging, 
and other symptoms of gastro-enteritis, mark its escharotic effects. 
Death from cedema of the larynx may occur within five minutes. 
More usually the fatal result is wrought out more slowly, with collapse 
and sometimes convulsions secondary upon the local effects. In some 
cases symptoms of impending suffocation, resulting in death from 
asphyxia, have occurred, and at the autopsy intense redness and 
congestion of the bronchial mucous membrane have been present, 
due no doubt to the irritant's having found its way into the bronchi. 
The intellect may be clear to the very moment of death, or stupor, 
and finally coma may be developed. If the victim survive for a few 
hours, recovery usually occurs, but the convalescence is commonly 
protracted, and permanent ill-health may result from the destructive 
lesions produced by the poison. These lesions are to be found not only 
in the respiratory and gastro-intestinal tracts, but also in the kidneys. 

The neutral salts of ammonium being only slightly irritant are much less actively 
toxic. Oesterlen affirms that he has seen two ounces of the chloride taken by man 
without the production of more serious results than violent gastro-intestinal pain 
and diarrhcea, while older observers state that two drachms of the salt are sufficient 
to cause death in a dog. According to Arnold, thirty grains will kill a rabbit in ten 
minutes; but Rabuteau found that one drachm injected intravenously produced 
in the dog only vomiting, muscular weakness, temporary paralysis of the hind legs, 
and general prostration, lasting four or five hours. When given for a length 
of time in very large doses it affects the general nutrition. We have seen extreme 
prostration and a typhoid condition apparently produced by the taking of half 
an ounce per diem for some days, while great prostration, with an eruption of bloody 
blebs, hematuria, and hemorrhages from the mucous membranes, has been reported 
by Isham as caused by the continuous use of the drug. 

The treatment of poisoning by ammonia consists in the neu- 
tralization of the ammonia as soon as possible by vinegar or other 
dilute acid, and the meeting of indications as they arise. If the 
cedema of the glottis be threatening, tracheotomy should at once be 
performed. 



CARDIAC STIMULANTS 187 

Administration. — As stated above, when ammonium is used as a 
circulatory stimulant it should be given hypodermically. For hypo- 
dermic use a water of ammonia or a solution of the ammonium 
carbonate is to be preferred. 

CAMPHOR. 

Camphor is a stearopten which is obtained in China, Japan and 
the neighboring islands by boiling the comminuted wood of the root 
of the Cinnamomum Camphora, a handsome evergreen tree which 
sometimes reaches a height of fifty or sixty feet. The camphor which 
arises to the surface of the boiling water is skimmed off and partially 
purified by sublimation — coming into commerce as crude camphor, 
which occurs in grains of a whitish or pinkish color — and is finally 
purified by sublimation with lime.* 

Refined camphor (or, as it is commonly called, camphor) occurs in 
disks or hemispherical bowl-like translucent masses, of a fibrous or 
granular fracture. Its taste is hot and peculiar; its odor very strong 
and characteristic; it is volatile, inflammable, tough, but readily 
pulverized on the addition of a few drops of alcohol; melts at 347° F.; 
is soluble in one thousand parts of cold water, f in one part of strong 
alcohol, and still more soluble in chloroform; thrown upon water, 
a granule of camphor floats, and exhibits a rotatory movement. 

Official Preparations : 

Camphora 5 to 15 grains (0.3-1.0 Gm.). 

Aqua Camphora? (0.8 per cent.) \ to 2 fluidounces (15-60 C.c). 

Spiritus Camphora? (10 per cent.) 15 to 30 minims (1-2 C.c). 

Camphora Monobromata 5 to 10 grains (0.3-0.6 Gm.). 

Linimentum Camphora? (Camphor 1 part, 

Cotton Seed Oil 4 parts) External use. 

Ceratum Camphora (10 per cent.) External use. 

Linimentum Saponis (4.5 per cent.) External use. 

Local Action, Absorption, and Elimination. — Camphor, though ' 
primarily a local irritant and stimulant, probably has a narcotic action 
on nerve-endings in the mucous membrane, in this way relieving 
intestinal spasm. It is slowly absorbed and in great part or altogether 
oxidized in the organism, probably changed first into camphorol, 
and being excreted in the urine as campho-glycuronic acid, and 
amido-glycuronic acid (Schmiedeberg and Meyer). 

Physiological Action. — The ordinary dose of camphor (five to 
fifteen grains) produces when taken internally a feeling of warmth 
in the stomach, with in some cases a sense of slight exhilaration and 
quietness, and some, but usually not a pronounced, acceleration of 

* Borneo camphor, yielded by the Dryobalanops Camphora, is very highly valued in the 
East, but does not reach this country. Stockman has found that both it and the Ngai comphor of 
China act on the organism like camphor. See Pellicani. A number of other camphors, such 
as Camphor-Cymol, Bornylamin, Amido-Camphor, Campherol, have been examined by various 
investigators, and found to resemble true camphor very closely in their physiological action. 

t By rubbing the camphor up with magnesia in water, the latter can be made to take up mucli 
more than one part in one thousand. 



188 GENERAL REMEDIES 

the pulse. In doses of from twenty to thirty grains it causes lassitude, 
giddiness, lessening of the pulse-rate, preceded in some cases by a 
brief period of excitement. 

Upon the lower forms of life camphor acts as a very feeble germicide; to the 
articulates it is a violent poison; in the frog it produces stupor with primary paraly- 
sis; in birds, according to Menghini, it causes stupor or delirium, with epilepti- 
form seizures; and in mammals vomiting, violent convulsions, coma, and death, 
apparently from asphyxia, follow its ingestion. 

Nervous System. — The precise action of camphor on the nervous 
system is not clearly understood. In the lower animals when given 
in ;i large dose it causes convulsions followed by paralysis. The 
convulsions are of cerebral origin. Upon the spinal cord the drug 
seems to act primarily as a mild stimulant and secondarily as 
a depressant. 

The convulsions which are caused by the toxic dose are certainly of cerebral 
origin, since C. Weidemann, Hoffmann (quoted by Weidemann), and Gottlieb 
have shown that they do not spread to the lower segment of the body after section 
of the cord; and R. Stockman has found that in the rabbit they do not occur 
after removal of the cerebral cortex. That the toxic dose finally produces cerebral 
paralysis is shown by the coma which is so frequent a symptom of camphor-poisoning. 

In the frog the regular course of paralytic symptoms produced by camphor 
are, first, loss of voluntary movement, the reflexes being intact; second, loss of 
reflexes, the muscles still responding when the motor nerves are stimulated; third, 
loss of function in the motor nerves, the muscles responding still to direct stimuli. 
It is probable that the loss of the power of voluntary movements is due to paralysis 
of the psycho-motor centres, although it may be the outcome of some interruption 
of the power of the cord to carry impulses from these centres to the motor cells in 
the cord. 

According to the experiments of Binz, Grisar, and Gottlieb, small doses of 
camphor increase reflex activity by a direct action upon the motor side of the spinal 
cord, but the experiments of Stockman appear to have yielded a different result, 
so that there is uncertainty in the matter. 

The toxic dose of camphor depresses the spinal cord, and, as was first shown 
by Weidemann, later the motor nerve-trunk, beginning with their peripheral endings. 

Muscles. — Upon the muscles themselves camphor exerts a very 
feeble influence. Locally applied to the muscles in the form of solu- 
tion or vapor, a notable effect is produced, but in general poisoning 
this is not evident. In experiments of Cesare Rossi, made with a 
Mosso's ergograph, camphor given internally seemed to distinctly 
increase the energy and endurance of the human muscle, but in other 
cases it entirely failed to manifest any such power; so that if it have 
any direct action as a muscle stimulant, such action must be feeble 
and uncertain. 

According to the experiments of Meyer, the absence of convulsions in camphor- 
poisoning in the frog cannot be explained by paralysis of the spinal cord or motor 
nerves, since before these conditions are developed the brain is profoundly affected; 
nor does the local application of camphor to the brain in the frog produce convul- 
sions. Meyer believes, with probable correctness, that the absence of convulsions 
is due to the rudimentary development of the cerebral system in the frog. 



CARDIAC STIMULANTS L89 

Respiration. — According to Stockman and Binz, camphor increases 
the rate of respiration greatly; and Lewin found that the amount of 
respired air moved was markedly increased in the rabbit by it. 

It would appear, therefore, that the moderate dose of camphor is 
a respiratory stimulant, and as there is probably some stimulation 
oi the cord by the drug, the inference is that such stimulation is due 
to an action upon the respiratory centres. The asphyxia of advancing 
camphor-poisoning indicates that the respiratory centres finally share 
with the other motor centres of the spinal cord the paralyzing influence 
of the overwhelming dose of the drug. 

Circulation. — Although clinical experience seems to indicate that 
camphor has a profound effect upon the circulation, our knowledge 
of its action is incomplete and uncertain. It has been directly shown 
by the concurrent experimental results of Heubner and Harnack and 
YVittkowski, Weidemann, Umpfenbach, Maki, and Stockman that 
the drug decreases the rate and increases the energy of the contractions 
of the isolated frog's heart,* and it may be considered established that 
upon the frog's heart camphor acts as a stimulant. 

On the other hand the evidences of stimulation of the heart in 
mammals is far from satisfactory. At times camphor, when injected 
in small doses directly into the circulation of a mammal, increases the 
arterial pressure, but this increase is never constant or persistent 
and is often absent, the characteristic effect of the camphor being 
depression of the arterial pressure. It is of course possible for a drug 
to stimulate the heart, and yet so widen the blood-path as to produce 
no increase in the arterial pressure; but although Gottlieb and Maki 
and Lewin believe that they have obtained evidence of cardiac stim- 
ulation, other observers have failed to do so. It probably, however, 
is a stimulant to the cardiac muscles and widens the blood-vessels, 
partly by an action on the vaso-motor centres and partly by a direct 
influence on the arterial walls. 

The statement of Heubner, that camphor will re-excite the movements of the 
frog's heart when arrested by muscarin, has been abundantly confirmed. Harnack 
and Wittkowski found that the atropine increases the contraction-rate of the cam- 
phorized heart, that stimulation neither of the vagus nor of the sinus is able to 
arrest cardiac contraction, and that muscle paralyzants like the soluble copper 
salts and apomorphine do stop the heart's beating. f Bohme found that camphor 
is capable of causing the heart arrested by chloral to recommence beating. The 
question whether the drug acts upon the muscle or upon the ganglia is still unan- 
swered, and certain actions of camphor upon the frog's heart are not easily explained. 
Thus, in Maki's experiments with Williams's apparatus, some minutes after the 
application of the camphor the blood-pressure fell below the norm, to rise very 
«hortly under very powerful pulsations of the heart. Then the blood-pressure would 
sink, to rise again in a little while, and again to sink. This alternation would occur 
several times. These experiments of Maki have apparently not been confirmed, 
but are especially interesting in relation with the periodic rise and fall of 
blood-pressure which lias been noted in mammals by Weidemann and others. 

* The contrary results of Alex. Lewin were probably due to the use of overwhelming doses, 
in such doses camphor certainly being a cardiac depressant. 

t In repeating Harnack and Wittkowski's experiments Stockman failed to get satisfactory 
results 



190 GENERAL REMEDIES . 

Stockman reached the conclusion that camphor depresses the vaso-motor 
centres and probably produces a vascular dilatation which masks the increased 
action of the heart, — a conclusion which is in accord with the statements of both 
Muki and Lewin, that in chloralized animals, when the vaso-motor centres are deeply- 
paralyzed, camphor elevates the pressure; but in Lewin's experiments, when the 
action of the chloral was profound, the pressure failed to rise under the influence of 
the camphor; and H. Winterberg determined that camphor does not raise the 
arterial pressure when chloral is given sufficiently to certainly paralyze the vaso- 
motor centres. Further, all attempts to demonstrate the stimulating action of 
camphor upon the more or less isolated heart of the mammal have so far yielded 
contradictory results. Gottlieb obtained an apparent stimulating influence from 
the camphor, but Winterberg, using the method of Langendorff for cardiac isola- 
tion, failed entirely, except in two experiments, to get any evidence whatever of 
cardiac stimulation. Seligman, although showing in some cases stimulation, was 
unable to demonstrate any constant influence on the normal mammalian heart, 
but found that camphor was capable of restoring coordinate beats to a heart thrown 
into fibrillary contraction.* 

As is shown by Weidemann, during the convulsive stage of camphor-poisoning 
there is a marked rise of the arterial pressure, which, however, may be prevented in 
great measure by curarization and artificial respiration, and is therefore evidently 
chiefly due to the convulsions and disturbances of breathing. In the curarized 
animal Weidemann found that camphor caused remarkable periodic alternating 
elevation and fall of the arterial pressure, which are prevented by section either of 
the cord or vagi, but whose nature Weidemann did not determine. Stockman 
found that, at least with Borneo camphor, such action is extremely inconstant, and 
Winterberg has demonstrated that when the curarization is complete the oscillatory 
phenomena are absent, so that they are probably due to obscure spasmodic 
movements. 

Sexual Function. — Camphor has been largely praised by some 
medical practitioners as a sexual stimulant, by others as a sexual 
depressant. Almost invariably, however, it has been administered 
in combination with other more potent drugs, to which any apparent 
influence of the remedy has probably been due. There is certainly 
no experimental and apparently no sufficient clinical reason for 
believing that camphor acts more decidedly upon the sexual centres 
of the spinal cord than it does upon other nerve-cells of the same region. 

SUMMARY. — Camphor causes convulsions through its effect 
upon the brain ; the therapeutic dose probably has a quieting influence 
on the cerebral cortex. In large doses it acts as a depressant to 
the motor cord, while the small doses are probably stimulant. It is 
a stimulant to the respiratory centres, and probably to the cardiac 
muscle, but does not greatly raise the blood-pressure on account of 
its "widening the blood-vessels, probably both peripherally and 
centrally. 

Therapeutics. — Camphor is very frequently given internally as 
an antispasmodic, to quiet restlessness and "nervousness." It is also 
employed in certain painful affections seen in those persons who are 
especially liable to the condition of the nervous system just men- 

* Rosenstein, in his research, concluded that camphor has a stimulating influence upon the 
heart, though a very fleeting one. With borneol, Pellicani obtained fall or periodical oscillations 
of pressure. Lewin was only able to obtain a fall of the arterial pressure, and Gottlieb reached the 
conclusion that probably camphor increases the capability of the heart to respond to stimuli, so 
that, while the normal systole is not altered, in pathological condition there is such an increased 
excitability that the heart is capable of great efforts. 



CARDIAC STIMULANTS I!)] 

tioned: thus, it is often useful in nervous headaches and dysmenor- 

rhcea. [ndeed, in the latter disease, either alone or combined with 
opium in had cases, it is a most valuable drug, but must be given 
freely. In diarrhoea not dependent upon inflammation, in nervous 
diarrhoea, in cholerine, and even to some extent in cholera, camphor is 
an efficient remedy, allaying intestinal pain and spasm, and also 
checking intestinal secretion. It enters into a large proportion of the 
popular cholera-mixtures. In sudden cardiac failure and in adynamic 
conditions it has been largely used, especially in Germany; but while 
it probably has distinct value when given hypodermically, it ought 
not to be relied upon to the exclusion of more potent drugs. According 
to Schilling, thirty grains a day may be given hypodermically in the 
profound adynamia of acute endocarditis, typhoid fever, pneumonia, 
etc., with the happiest result. In our experience its action in these 
states has been, though prompt and marked, but a transient one. 
The use of large doses of camphor in abnormal sexual excitement, and 
in chordee, has about passed out of vogue, which also is true of its 
employment in severe convulsive disorders such as whooping-cough, 
epilepsy, and puerperal convidsions. In hysterical convulsions, as in 
other phenomena of similar origin, camphor is a useful antispasmodic. 

Externally, camphor is much used in liniments as a stimulant 
application for bruises, sprains, etc. 

Toxicology. — After poisonous doses of camphor the symptoms, 
which are tolerably uniform, are as follows: faintness, headache, 
vertigo, confusion of ideas, burning pain in the stomach, dyspnoea, 
delirium, spasms deepening into violent convulsions, coma, with 
complete insensibility and absence of all reflexes; the pulse, at first 
full and quick, later becomes small and sometimes slow; the skin is 
cool, pale or livid, generally bedewed with sweat. Glycosuria has been 
noted by Stockman. Sudden unconsciousness, with or without 
convulsions, has been in some instances the first manifestation of the 
action of the poison, and in any individual case many of the symptoms 
detailed above may be wanting. Although camphor has in many 
cases produced very alarming symptoms, over two hundred grains 
of it have been taken without permanent result, and the recorded 
fatal poisonings are very few. The only ones known to us are — 
adult, quantity unknown; sickly infant, ten grains; child two 
years old, unknown amount; fatal abortion produced by three 
drachms.* 

Administration. — Large doses (ten to fifteen grains) of camphor 
are best administered in emulsion, because when given in this way, 
being very finely subdivided, they create as little irritation as possible, 
and are rapidly absorbed; smaller doses may be given in pill. For 
hypodermic use a ten-per-cent. solution in olive oil should be preferred. 
As an antispasmodic, the Camphor Water is usually preferred. 

* Cases, Edinburgh Med. Journal, Mav, 1873; The Clinic, March, 1873; Wiener Medizinische 
Presse, 1874, 258; Berlin. Klin. iVochens., Sept.. 1873-74; Trans. Land. Clin. Soc, 1874, 27; London 
Lancet. 1876, ii. 71; British Med. Journ., Feb. 1875; 1877, i. 607; Sept. 189.5; June, 1896; St. 
Petersburg Med. Wochens., 1897, xiv.; Austral. M. J., June, 1888; N. Y. M. R., March, 1887. 



192 GENERAL REMEDIES 

The Oil of Camphor occurs in our market as a reddish or yellowish-brown liquid, 
having a strong odor of camphor, and a hot, camphoraceous taste. It contains 
camphor in solution, and is probably equivalent to it in physiological action, except 
that it is locally more stimulating, and preferable in intestinal disorders. Dose, 
five to ten minims (0.3-0.6 C.c). 

Camphoric Acid (Acidum Camphoricum) is produced by boiling camphor with 
concentrated nitric acid. It occurs in small white, acicular or scaly crystals, free 
from odor, of a feebly acid taste, sparingly soluble in cold, freely in hot, water, 
also in alcohol, ether, and fatty oils. It was originally proposed by Furbringer as 
an antiseptic of practical value for the disinfection of the intestinal canal, and in 
the treatment of tuberculosis and ammoniacal cystitis: as first noticed by Witt- 
kowski it is a very valuable antihydrotic in the night-sweats of phthisis; how it 
acts in these cases lias not been determined. Max Reichert, Niesel, and other 
physicians have found it very serviceable as a local application in the treatment of 
tubercular and other catarrhs of the upper and lower air-passages. 

According to Fujitani, sodium camphorate acts as a depressant to the motor 
side of the spinal cord and is also stimulant to the heart. The evidence he presents 
of the last fact, however, is not convincing. Bohland asserts that camphoric acid 
is rapidly eliminated, the whole of a single dose escaping from the kidneys in the 
course of five hours unaltered. In cystitis, fifteen grains (1 Gm.) may be given three 
or four times a day; for night-sweats, fifteen to thirty grains may be administered 
at bedtime, or, when the sweat occurs late in the night, the dose may be divided, 
the patient being wakened to take the last dose after midnight. Gastric irritation 
and even vomiting have been noted after thirty grains, and Niesel saw severe renal 
irritation in a patient who had taken in four weeks fifty grammes. 

Oxycamphor. — This oxidation product of camphor is a white, crystalline powder, 
soluble to two per cent, in cold water; is alleged to have a calmative action upon 
the respiratory centres while strengthening the cardiac muscle and the central and 
peripheral vaso-motor nervous system. It has been used with asserted excellent 
results in dyspnaa from cardiac weakness, and from tubercular and other chronic 
diseases of the lungs. Dose, eight to fifteen grains (0.5 to 1 Gm.) 

ALCOHOL. 

Absolute Alcohol, — i.e., ethyl alcohol containing not more than 
one per cent, by weight of water, — is a colorless, volatile liquid, boiling 
at 172° F., not congealed by a cold of — 166° F., and having the 
specific gravity of 0.797. It is used only for chemical purposes. 
Alcohol of the Pharmacopoeia contains 94.9 per cent., by volume, of 
absolute ethyl alcohol, and has the specific gravity of 0.816; Diluted 
Alcohol contains 48.9 per cent., by volume, of absolute ethyl alcohol. 

Alcohol also exists in Whisky and Brandy, which are obtained 
respectively by the distillation of fermented grain and of fermented 
grapes, and should contain from forty-five to fifty-five per cent, of abso- 
lute alcohol, and in the official Red Wine and White Wine. For 
medicinal use, brandy should be at least four and whisky two years old. 

Official Preparations : 

Alcohol (95 per cent.). 

Alcohol Absolut um (99 per cent.). 

Alcohol Dilutum (49 per cent.). 

Spiritus Frumenti [Whisky] (44 to 55 per cent.). 

Spiritus Vini Gallici [Brandy] (44 to 55 per cent.). 

Vinum Album. 

Vinum Rubrum. 



CARDIAC 1 STIMULANTS L93 

Local Action.-- Alcohol is an active irritant, but is not corro- 
sive. It is also a pronounced germicide, which when in proper 
concentration is capable of killing all protoplasms. 

According to the researches of C. Harrington and H. Walker, against dry 
bacteria absolute alcohol and ordinary commercial alcohol are wholly devoid of 
bactericidal power, while forty-per-cent. alcohol is effective within five minutes 
against most non-sporulating pathogenic bacteria. In order to destroy some of the 
strongly resisting bacteria, w he1 her dry or moist, sixty- to seven ty-per-cent. alcohol 
is necessary. Preparations of alcohol more concentrated than seventy per cent, do 
not, however, act more powerfully upon bacteria than do the weaker preparations, 
so that for the practical disinfection of a wound sixty- to seventy-per-cent. alcohol 
should be preferred; the contact should be maintained for at least five minutes. 

Absorption and Elimination. — Alcohol is absorbed with great 
rapidity by the stomach, but, as has been shown by Von Mering, is 
also hurried on into the intestines. It is without doubt taken up 
freely into the whole length of the alimentary tract. In Baum's 
experiments symptoms of intoxication appeared in a horse fifteen 
minutes after its injection into the rectum. (For a study of the point 
of elimination in the system, see page 198.) 

Physiological Action. — Nervous System. — We have not met with 
a close experimental study of the order in which the nervous centres 
are affected, but it is scarcely doubtful that alcohol acts upon them 
as does ether, except that the latter substance, being much more 
volatile than alcohol, is consequently absorbed and eliminated much 
more rapidly, so that its influence is more evanescent. We know by 
experiment that the vapor of alcohol is capable of producing the 
stupor known as anesthesia, and, further, that this anesthesia may be 
deepened into death, accompanied by all the phenomena of fatal 
ether-narcosis. There has been, in the past, much discussion as to 
whether the small dose of alcohol had a stimulant action on the 
intellectual centres. Without going into details, in our opinion, there 
seems to be no satisfactory evidence that alcohol in any dose is a 
true cerebral stimulant. The increased garrulity of the alcoholic is 
due to a paralysis of the will rather than a stimulation of the mind. 
The observation of Dogiel, that in the alcoholized dog both sensory 
and motor nerves are markedly depressed, without doubt holds good 
for acute alcoholism in man. Whether this depression is due directly 
to the alcohol or to the changes produced by it is uncertain. It cannot 
be denied that the continuous effect of large doses of alcohol upon the 
nervous tissue is depressant. 

The original experiments of Heinrich Dehio, showing that changes 
can be demonstrated in the ganglionic cells of the brain in animals 
killed by the large dose of alcohol, have been repeated and extended 
by Colin C. Stewart with corroborative results. 

Circulation. — The action of alcohol upon the circulation has been 
the subject of a great deal of investigation and dispute. Much of the 
evidence is so contradictory that positive conclusions are very dif- 
ficult. We believe, however, that from the mass of investigation it 
13 



194 GENERAL REMEDIES 

ma)' be fairly deduced, that in moderate doses alcohol has a slight 
stimulant influence upon the cardiac muscle, and at the same time 
it produces a dilatation of the blood-vessels of the skin; these 
actions may so counter-balance each other that there is little or 
no change in the blood-pressure, although there is evidence that in 
many cases alcohol may produce a slight rise of pressure. After exhi- 
bition of large doses, the drug acts as a depressant to the heart and 
also widens the vessels, probably through direct influence as well as 
an effect upon the vaso-motor centres. 

Much of the evidence concerning the physiological action of alcohol is entirely 
useless on account of the size of the closes which were applied. Although a number of 
experimenters have failed to obtain a rise of blood-pressure from any dose of alcohol, 
yet various investigators, as Dogiel, Castillo, Kochmann, Eagleton, Bachen and 
Dixon, have all noted more or less marked elevation of the pressure from the injec- 
tion of alcohol. According to Dixon the failure to obtain rise of pressure by many 
observers has been due to the action of the anesthetic which was employed. In the 
experiments of H. C. Wood and D. M. Hoyt, although in the majority of cases alcohol 
failed to produce rise of pressure, in certain instances there was a distinct elevation 
of the blood-pressure. Those who have investigated the question are almost unani- 
mous that, after section of the spinal cord, there is a distinct rise of pressure. This 
fact, which was originally noted by Castillo, has been confirmed by Abel and by Wood 
and Hoyt-, and would point very strongly to the increase in the cardiac activity. 

Studies have been made upon the isolated frog's heart by Umpfenbach (1881), 
by Ringer and Sainsbury (1883), by Maki (1884), and by Dresser (1888), with the 
general conclusion that alcohol is a direct depressant to the cardiac muscle; while 
Castillo (1880), Eagleton and Cerna have reached opposite conclusions; so that the 
present experimental evidence on the subject is contradictory so far as the isolated 
frog's heart is concerned. According to Wood and Hoyt- most of this evidence is 
unavailable because of the lack of delicacy of the methods employed, and in their 
experiments they obtained, uniformly, evidence of stimulation of the frog's heart. 
Martin, Hemmeter, and Kochmann in experiments upon the isolated mammalian 
heart were unable to observe any evidence of increased work. Upon the other 
hand, Bachen, Loeb, Dixon and Bachmann, all obtained evidence of the increased 
action of the warm-blooded heart under the influence of alcohol. According to 
Bachmann and to Dixon, this stimulation is similar to that which is caused by the 
addition of glucose to Ringer's fluid and they believe that it is a result of food upon 
the heart -muscle. The theory that the blood-pressure is not affected by alcohol, 
despite the stimulation of the heart, on account of the widening of the vessels, is 
further borne out by the observations of Hemmeter and by Wood and Hoyt — that 
alcohol increases the velocity at which the blood flows through the vessels and 
by the sphygmographic experiments of Wood and Hoyt. 

The studies of the effect of alcohol upon the circulation of the human being 
are mostly lacking in sufficient accuracy to make them of scientific value; but 
Cabot and Binz in sphygmomanometric observations fail to discover any rise of 
blood-pressure. On the other hand Kochmann, with doses of from five to ten C.c. 
of absolute alcohol, obtained uniformly a distinct rise in the blood-pressure; larger 
quantities than this produced a greater or lesser fall, according to the dose. 

Blood. — There seems to be little reason for supposing that alcohol 
in therapeutic dose has an appreciable effect upon the blood, but as 
long ago as 1841 C. H. Schulz observed that mixed with the blood 
outside of the body it not only causes coagulation, but also separation 
of the hemoglobin from the corpuscles. It is probable that to the 
action of the alcohol upon the hemoglobin is due the fact noted by 



CARDIAC STIMULANTS 1!),-, 

Schmiedeberg that alcohol mixed with blood lessens its ability to 
yield oxygen in the presence of a reducing agent, .bullet and Hayem 
state that in rapid alcoholic-poisoning in animals extensive alteration 
in the blood-corpuscles can be discovered, many of these bodies 
being shrivelled and altered in form, with yellow precipitates of 
hemoglobin in their interior. 

Temperature. — Owing no doubt to the sensations of warmth 
induced by its local action on the stomach and by the increased 
activity of the circulation in the extremities, alcohol was formerly 
looked upon as a promoter of animal heat. This view was questioned 
as early as 1S4N by Dumeril and Demarquay, and has been studied 
and written about to an enormous extent. The matter has been so 
thoroughly worked out that it does not seem wise to do more 
here than give results, and to refer the reader who is desirous of 
following up the literature of this subject to the tenth edition of 
this treatise. 

In the lower animals small doses of alcohol produce a slight 
increase of the bodily temperature, which rarely in mammals reaches 
more than 1° F. Larger doses of alcohol produce a fall of tempera- 
ture in the animal proportionate to the size of the dose. According 
to Ruge, when the dose has not been sufficient to cause distinct 
intoxication, the fall usually amounts to from |° C. to f° C, rarely 
reaching one degree. When there is distinct narcosis the fall may 
amount to 3° C, or with a lethal dose to 5° C. Bouvier and other 
observers have found that the effects of large doses of alcohol are even 
more marked in animals suffering from pyemic fever; the reduction 
of temperature may amount to 8.5° C, and the fever be altogether 
put aside by the narcotic dose. The effect of alcohol upon the tem- 
perature in man is parallel to that which is produced in the lower 
animals; the fall from large doses is, however, less pronounced, 
probably because the cerebrum of man is proportionately much more 
sensitive to alcohol than is that of the animal, and narcosis results 
from smaller doses of the poison. Again, in persons accustomed to 
the use of alcohol the elevation of the temperature does not appear; 
and, indeed, it cannot always be produced in a normal subject. Fur- 
ther, the habitual use of alcoholic stimulants greatly lessens the 
depressing influence of alcohol upon the bodily temperature, so that 
the temperature of the drunken man is not always below the normal. 
As, however, intoxication becomes more profound the tendency to 
a fall of temperature is more and more marked. 

The fall of temperature produced by alcohol is largely due to an 
excessive loss of heat, but the relations of alcohol to thermogenesis 
form such an integrant portion of its action on nutrition that its 
discussion will be postponed to that heading. 

Respiration. — According to the experiments of Binz, of Fonteyne 
and of A. Jaquet, small doses of alcohol increase the number and 
amplitude of the respiratory movements. The toxic dose of alcohol 
decreases the respiratory air movement. The drift of the present 



196 GENERAL REMEDIES 

evidence is to show that the action is centric, and that alcohol stimu- 
lates or paralyzes the respiratory centres according as it is in small 
or large amount. 

Jaquet certainly failed (o prove the truth of his conclusion that the increase of 
respiratory movement produced by alcohol is due to local irritation; and in a later 
research Binz, by means of controlled experiments, apparently demonstrated the 
incorrectness of Jaquet's theory. Binz lias extended his experiments not only to 
the lower animals, but also to man, in whom he found that the increase of the respi- 
ration is distinct although not very large, and is much more pronounced in those 
who have been previously fatigued. 

Nutrition. — The question of the effect of alcohol upon the nutri- 
tion divides itself naturally into two sub-questions: Its direct drug- 
action upon the chemical processes of the body, and its possible food 
value as an oxidizable hydrocarbon. 

In regard to the first point, as the result of a vast amount of 
experimentation, much of which is contradictory, it appears that the 
only fair conclusion is that alcohol has very little if any direct action 
upon the heat production, or the elimination of carbonic acid or 
nitrogenous waste products. 

In regard to the possible food value of alcohol, it may be consid- 
ered to-day as proven that a small dose of alcohol, corresponding 
to about three ounces of absolute alcohol, is practically entirely 
oxidized in the sj'stem, only about one to five per cent, escaping 
consumption. Second, that the result of this burning up of alcohol 
is the production of energy which may be utilized to a certain extent 
by the economy, and lessen the oxidation of the bodily tissues; or, 
if looked at from another point of view, diminish the amount of 
hydrocarbon food necessary to maintain nutritive equilibrium. To 
this extent, therefore, alcohol must be regarded as a food, that is, 
as a substance which the system is capable of oxidizing for the pro- 
duction of useful energy. On the other hand, it would seem estab- 
lished that alcohol is not capable of being stored up as a reserve food, 
that is, not only can it not enter into the composition of the proteid 
tissues of the body, but unlike fatty foods and the starches, it cannot 
add to the amount of fat in the system, except indirectly by offering 
a more easily oxidizable substance and thus preventing the burning 
up of the other hydrocarbon elements of the food. 

The attempts to determine the action of alcohol on metabolism by studying 
heat formation have failed to produce any evidence of a positive effect. 

The first calorimetrical studies upon alcohol were those by Bevan Lewis. He 
found that in the rabbit alcohol sometimes produces a primary lessening of heat- 
production, most marked and pronounced after small doses, followed by a marked 
increase in heat-production, most pronounced after large doses of the alcohol. In 
five observations by E. T. Reichert and H. C. Wood upon dogs, the average results 
were in accord with those by Bevan Lewis, although their individual experiments 
yielded somewhat varying results. In some of these experiments heat-dissipation 
more than kept pace with the increase of heat-production, and the bodily tempera- 
ture fell. In other instances the bodily temperature rose, showing that heat-produc- 
tion was increased more than heat-dissipation. In a further series of experiments 



CARDIAC STIMULANTS 197 

E. T. Reichert obtained, in five experiments, increased heat-production, and in 
thirteen decreased heat-production, the difference not depending upon dose, and 
tlic range of variation of result being as much as sixty-five per cent., a strong 
indication thai there was something wrong with t lie method or the experiments. 

These results are somewhat discordant and varying, hut certainly indicate that 
alcohol has no such immediate dominating influence upon tissue change as greatly 
to increase heat-production. The fall of bodily temperature which occurs after 
toxic doses of the drug is without doubt due to an excessive heat-dissipation, which 
in turn is the result of vaso-motor paralysis, and the mere excessive loss of heat has 
a profound influence in provoking increased heat-production just as increased heat- 
production lias a profound influence in inducing increased heat-dissipation; so that 
much care is necessary in the consideration of calorimetrical studies of large doses 
of vaso-motor paralyzants. But if the action of alcohol were pronounced it should 
manifest itself over all indirect and disturbing influences. On the whole, therefore, 
the earlier calorimetrical studies indicate that alcohol does not pronouncedly and 
directly affect those nutritive processes through which the animal heat is maintained, 
a conclusion which is confirmed in the very elaborate memoir of Atwater and Bene- 
dict, who, using small doses of alcohol, found that in man the increased heat-pro- 
duct ion was no greater than could be accounted for by the potential energy of the 
alcohol oxidized. 

The effect of alcohol upon the elimination of carbonic acid by the lungs has 
been investigated by several observers, with different results. 

According to the researches of Bocker, of N. S. Davis, of Hammond, of Perrin, 
of Boeck and Bauer, of Rumpf, and of Bodliinder, there is a lessening in the amount 
of carbonic acid gas exhaled. On the other hand Henrique, Wolfers and Zuntz 
obtained evidence of increased carbonic acid elimination; E. Smith found that 
small doses of alcohol increased the elimination of the gas, although brandy, whisky, 
and gin always lessened the production. 

If alcohol really did have a direct powerful influence upon oxidation in the 
general system the conclusions of investigators should be more in accord, and it 
would seem, therefore, improbable that alcohol has any marked action on the 
carbonaceous metabolism. 

The determination of the action of the drug upon the chemical movements 
of protoplasm, and the destruction of albuminous materials in the body, is of course 
to be made by a study of its effect on the nitrogenous elimination. 

The studies on the elimination of nitrogenous waste products, made by Riess, 
Keller, Munk, Norris and Smith, and Rosenfeld indicate — despite the contrary 
results obtained by Donogany and Tibald — that alcohol diminishes slightly the 
quantity of urea excreted. This effect is, however, no more than might be expected 
from the addition of an oxidizable hydrocarbon food to the dietary. In Rosen- 
feld's experiments nitrogenous equilibrium having been produced in a man, alcohol 
was given with the result that the amount of nitrogen eliminated was markedly 
decreased; after this period sugar was substituted for alcohol, and the eliminated 
nitrogen still remained lower than the intake. During the alcohol period the amount 
of uric acid eliminated was distinctly above the normal; during the sugar period 
this was not the case. Rosenfeld concludes that since uric acid arises generally 
from the nucleated albumin, the alcohol has spared the nuclein-free proteid tissues 
at the expense of the nucleo-albumins. According to Beebe, when alcohol is taken 
in conjunction with purin-free diet, the proportion of the uric acid in the urine is 
not augmented, but when the diet contains this type of food-stuff the uric acid excre- 
tion is increased. He interprets these residts to mean that the drug interferes with 
the function of the liver to prevent the complete oxidation of nuclein foods to urea. 

Beebe's results have, how'ever, been contradicted by Jackson and Blackfane, 
who find that, even on a diet free from all nitrogenous foods, the elimination of uric 
acid is increased, the urea and total nitrogen remaining unaffected. 

In studying the question of the possible food value the first thing 
is to determine whether alcohol is oxidized in the system. This 



IDS GENERAL REMEDIES 

question has been investigated by Baudot, Schulinus, Lieben, Anstie, 
Thudichum, Subbotin, Edes, Bodlander, and Strassmann. with con- 
cordant results. After moderate doses of alcohol from one to two 
per cent, can be recovered from the urine and about an equal 
quantity in the breath, and, as no aldehyde or other alcohol deriva- 
tive can be found in the body, it must be concluded that from ninety- 
five to ninety-eight per cent, is completely oxidized into carbonic 
acid and water. 

A. Benedicenti finds that an increase in the amount of ingested alcohol does 
not greatly influence the elimination through the lungs, but that lowered tempera- 
ture markedly lessens such elimination. Abelous, Bardier and Ribaut found that 
when alcohol is given in from one to tlu - ee C.c. per kilo in the warm-blooded animals 
from eighty-seven to ninety per cent, of it is destroyed within eight hours. In the 
frog ninety per cent, of the alcohol injected could be recovered from the body under 
four days; after seven days, however, none remained in the system. Finally, W. 
0. Atwater and F. G. Benedict, as the result of elaborate studies made upon human 
beings in a respiratory chamber, found that when an amount of alcohol correspond- 
ing to six ounces of whisky was taken, the average elimination was one and 
nine-tenths per cent. 

A further confirmation of the theory that asserts the oxidation of alcohol in 
the body is found in the experiments of H. Ford, which, if accurate, demonstrate 
that alcohol is formed in the body out of hepatic sugar. 

Working on a very large scale, by the distillation of the blood of animals, Ford 
obtained in weighable quantities a substance which he believed to be alcohol.* 
Further, Ford distilled various tissues, also blood from the lungs and liver. He also 
made elaborate calculations, based on the carbon ingested and on the carbon ex- 
haled, as to the amount of alcohol which ought to be found in the capillary blood 
of the lungs, and found experimentally quantities corresponding to his calculations. 
He found that the smallest quantity of alcohol is to be obtained from fresh 
liver-tissue, and the greatest from putrescent liver-tissue, in which the glycogen 
must have undergone fermentation. 

These researches of Ford are corroborated by the discovery, first made, we 
believe, by A. Lieben, although usually attributed to Dupre, that a substance exactly 
resembling alcohol exists in very minute quantity in the urine even of teetotalers.! 
M. Bechamp, apparently without a knowledge of the work of the other chemists, 
obtained, from the urine of persons who had not taken any alcoholic beverage for 
a long time, alcohol in sufficient quantity to burn it. As Lieben also found that 
this substance exists in the urine of dogs, horses, and lions, and as A. Rajewski 
obtained it from healthy rabbits, and as further, Hoppe-Seyler (quoted by Bowditch 
and Hodge) states, "traces of alcohol are found in human organisms such as the 
brain, muscles, liver, not only after alcoholic indulgence but without this they seem 
to be constantly present," it appears to have been proven that alcohol is found in 
the normal human organism, and probably subserves some need of the processes 
of the body.J 

If alcohol be oxidized in the body, it must of course generate force, measurable 
by the modern standard of the heat-unit. A little calculation will show the impor- 

* Space is wanting to describe in detail the very elaborate methods employed by Ford. The 
tests which he relied on, to prove that the liquid obtained was alcohol, were the chromic acid test, 
the peculiar inflammability, and the optical appearance of the alcohol in the conducting-tubes 
at the time the distillate commenced to boil. 

t It has been asserted that the substance "is not alcohol. It passes over among the earliest 
products of distillation, yields acetic acid on being oxidized, reduces the potassium dichromate 
when dilute sulphuric acid is present, and its aqueous solution has a lower density than water. 
It furnishes iodoform, and exists in the urine in a very small quantity." Possessing the physical 
and chemical characters of alcohol, to ordinary minds it is alcohol. 

+ Doming and Praetorius found that fecal matter on decomposition yielded alcohol to such an 
extent as to suggest a possible remunerative source. Von Meyer and O. Mohr, working indepen- 
dently, found that the amount of alcohol in the fecal matter was too small for commercial product 
(Chem. Centralb., 1904, 1. 030). 



CARDIAC STIMULANTS 199 

bance, or rather the great amount, of the generated force. According to Dupre.one 
gramme of alcohol oxidised in the body evolves 7 is l units <>f heat, while the same 
weight of lean beef gives off only 1482 units of heat. It has been estimated thai 
9.3 ounces of lean beef equal to about two ounces of alcohol — will supply the 

necessary force to maintain the circulation and respiration of an average man for 
One day. 'That is, four ounces of strong spirit will suffice for this purpose. 

The ergographic studies made by Lombard, Kraepelin, Sehcffer, and other 
investigators, afford no proof that alcohol in moderate close has a direct action upon 
the working power of the muscle. An underlying, almost unsurmountable difficulty 
in this method of experimentation is the impossibility of separating the indirect 
from the direct effects of alcohol. The experiments which have been made with 
the isolated frog's muscle indicate that alcohol has, when in appropriate dose, a 
direct stimulant effect either upon the intra-muscular nerve-endings or the sar- 
oolemma. Further, when there is a lack of sufficient food, alcohol seems to be espe- 
cially useful for the purpose of increasing muscular power and probably is used by 
the muscle as power-source. Large doses of alcohol depress the muscle; apparently 
its action upon voluntary muscle is very similar to its influence upon the 
heart -muscle. 

Lombard Warren found that small doses of alcohol increased, larger doses 
diminished, his muscular power. Dastre found that alcohol first temporarily in- 
creased, afterwards depressed, the muscle, so that the w : hole muscular work done 
when under its influence was less than normal. In H. Frey's studies the alcohol 
lessened the working power of the normal muscle, but markedly refreshed the 
nearly exhausted muscle, a refreshment which Frey believes to be due to the alcohol 
supplying an oxidizable material to the muscle which had exhausted its stored-up 
force-producing material. Sehcffer reached the conclusion that alcohol at first 
increases the muscular working power and shortly afterwards diminishes it. 
Schnyder determined that alcohol in small quantities, taken by the individual when 
tired and in a fasting condition, exerts a favorable influence upon the force of the 
muscles; an influence, however, which is less than that of ordinary food of equal 
caloric value; also, further, that when there is an abundance of food, alcohol fails 
to make itself manifest; and in any case if in large amount, by its action upon 
the nervous system depresses muscular force. F. S. Lee and W. Salant found that 
dilute alcohol, about forty parts by weight to one thousand of the frog, quickened 
both contraction and relaxation, delayed fatigue, and increased the amount of 
work possible to the isolated muscle. 

These considerations warrant the statement that in a certain sense 
alcohol is a food, — i.e., that it is capable of being used for the -purpose 
of the organism; but it does not necessarily follow from this that 
alcohol is capable of replacing fats and hydrocarbons in food. In 
attempting the determination of this, two methods have been used, 
— that of Von Noorden and that of Atwater- 

According to the Method of Von Noorden the individual is brought into a con- 
dition of nitrogenous equilibrium by careful feeding, and when this condition has 
been thoroughly established, non-nitrogenous articles of food are withdrawn and 
alcohol substituted in isodynarnic quantity. Under such circumstances, if the 
alcohol be superior to the hydrocarbon in replacing the nitrogenous material, less 
nitrogen should be eliminated than before its administration; if the power of the 
alcohol be less than that of the hydrocarbon, more nitrogen would be thrown off; 
if the alcohol just replaced the hydrocarbon, the nitrogenous equilibrium would 
not be disturbed. 

Stammreich's experiments upon himself were tw T o in number. In the first 
experiment there was a distinct lessening of the elimination of nitrogen during the 
alcohol period, showing that the alcohol replaced the nitrogenous material more 
actively than the corresponding fat mass for which it had been substituted. In the 



200 GENERAL REMEDIES 

second experiment, with a lessened amount of nitrogen in the food, there was at 
first no pronounced change in the nitrogenous elimination, followed, however, after 
two days by a marked increase, which continued for three days after the withdrawal 
of the alcohol. A third set of experiments were made with very little nitrogen in 
the food. Under these circumstances there was a great increase of the elimination 
of nitrogen during the alcohol period. 

As the result of the comparison of various experiments Von Noorden reached 
the conclusion that when the food is rich in albuminous compounds, alcohol is 
able to replace hydrocarbon or fats; but when the food is poor in albumin, it cannot 
do so. A similar series of experiments have been made by K. Miura. In the experi- 
ments — in which food with but little nitrogen was given — the results obtained by 
Miura were similar to those of Stammreich. On the other hand, in opposition to 
Stammreich, Miura found that when the food is rich in albuminous material, alcohol 
is not able to replace the non-nitrogenous foods. Miura believes that these differ- 
ences depend in part upon the facts that in Stammreich's experiments the alcohol 
was substituted for fats, while in his experiments it replaced carbohydrates, which, 
according to Voit, have greater power of sparing the nitrogen materials than have 
the fats; so that alcohol might be equivalent to fats and yet not to carbohydrates. 
Neumann, after producing in himself nitrogenous equilibrium, omitted half of the 
fat from his diet, causing thereby nitrogenous loss. By substituting alcohol for the 
fat he found that there was a return to nitrogenous equilibrium. In a subsequent 
period, after re-establishment of nitrogenous equilibrium, he added alcohol in doses 
increasing up to one hundred grammes a day, with pronounced nitrogenous gain. 
In a third period, the alcohol was continued, but a part of the fat was withdrawn, 
which caused a slight nitrogenous balance. From these experiments Neumann 
concludes that alcohol has the property of sparing the proteids, but is probably not 
capable of entirely replacing the fats. 

In the extraordinarily elaborate research made by W. O. Atwater and F. G. 
Benedict,* three selected men were kept for periods varying from five to nine days 
in a respiration calorimeter, in such a way that the heat-production and all the 
excretions from the body, liquid and solid, could be studied. On some days no 
exercise was taken; on others by means of a stationary bicycle, a large amount of 
measured work was done. The diet was regulated with scientific accuracy. On the 
alcoholic day one gramme per kilogramme of bodily weight of alcohol was taken 
in six doses; a quantity of alcohol which seems small but whose potential energy 
was about one-fifth of the total diet energy in the rest-period, and one-seventh of 
the total diet energy in the work-period. It was determined in these experiments 
that the potential energy of the alcohol was transformed by the body into kinetic 
energy as completely as was that of the ordinary nutrients; also that the efficiency 
of alcohol in the protection of body-fat was equal to that of the corresponding non- 
alcoholic diet; alcohol, isodynamic amounts of fats and other carbohydrates having, 
therefore, equal protective power against loss of fat. The efficiency of the alcohol 
in protecting the protein of the body was evident but usually not entirely equal to 
that of isodynamic amounts of ordinary nutrients, although in some of the 
experiments alcohol seemed to protect protein equally with ordinary food. 

In regard to muscular work, the experiments seem to show that the total energy 
of the ordinary diet is utilized a little more thoroughly than is that of alcohol, but 
the difference was so small as to be entirely within the limits of experimental error; 
it was. on the average, less than one per cent, of total energy, and is, therefore, of 
very little importance. 

It is proven that alcohol when taken in moderate amount is 
oxidized in the body, and in this process of oxidation it must yield 

* The research of Atwater and Benedict deserves much more thorough discussion than can 
be given in the text of this book. It seems to us most remarkable in conception and execution, and 
for the present at least these results ought to be taken as conclusive. The method employed in 
its directness is in our thinking far more likely to yield the truth than is the indirect plan of pro- 
ducing nitrogenous equilibrium. The number and extent of the experiments also are out of 
comparison with those of the early workers. 



CARDIAC STIMULANTS 201 

kinetic or active energy. The researches which have just been epito- 
mized seem to us to definitely determine that this kinetic or active 
energy is employed by the organism for life purposes, and that alcohol 
must be considered as a food capable to some extent of replacing hydro- 
carbons. It must be remembered in applying this scientific knowledge, 
however, that the organism can only consume a limited amount of 
alcohol, and that, therefore, the food value of alcohol has narrow 
limitations. 

Digestion. — It is definitely proven that alcohol when in small 
amount outside of the body does not markedly affect the activity 
of the digestive ferments, yet, in the living animal, by provoking- 
secretion, by increasing peristaltic activity, or in other ways it may 
really stimulate natural digestion. In larger quantities — more than 
ten per cent. — it markedly inhibits the digestive power of the fer- 
ments. The alcoholic beverages influence digestion through some 
other principle than the alcohol contained, for it has been shown 
that the malt liquors lessen the activity of peptenzyme out of all 
proportion to their alcoholic content, and that the wines are also more 
harmful to digestion than a corresponding amount of pure alcohol. 

The laboratory researches of W. Buchner, of R. H. Chittenden and L. B. Mendel, 
and of William Roberts are concordant and conclusive. The results reached are 
as follows: Salivary digestion is not very actively affected by the presence of pure 
alcohol; indeed, when there is not more than four or five per cent, the digestive 
power of ptyalin seems to be increased: ten per cent, of absolute alcohol (i.e., 
twenty per cent, of proof-spirit) retards it slowly. On the other hand, wines and 
malt liquors very greatly hamper salivary digestion almost in exact proportion 
to their degree of acidity. Pure alcohol seems to increase rather than diminish 
gastric-juice digestion until the amount rises to two or three per cent.; less than 
ten per cent, appears not to be constantly and demonstrably inhibitive; after twenty 
per cent, the digestive action may be reduced to one-third. A very important 
fact is that the retardation produced by a given percentage of alcohol varies greatly 
with the activity of the ferment and the nature of the material to be digested. 
Chittenden and Mendel have found that three per cent, of alcohol distinctly retards 
the proteolytic action of the pancreatic juice, while, according to A. Dastre, fifteen 
per cent, puts an end to the artificial pancreatic digestion of nitrogenous materials. 

Chittenden, Mendel, and Jackson found that alcohol temporarily increases the 
flow of saliva reflexly by its irritant influence upon the mucous membranes of the 
mouth; and that it increases the secretion of gastric juice very greatly, the action 
on the stomach being exerted not only by alcoholic fluids in the stomach but by 
absorbed alcohol. They further determined that the ordinary alcoholic drinks agree 
in stimulating gastric secretion, and that the gastric juice secreted was stronger in 
hydrochloric acid and in proteolytic power than normal. It is worthy of note that 
in experiments made by Chittenden upon healthy dogs with gastric fistulas, using 
proteid test-meals, digestion was never retarded nor accelerated, leading to the 
conclusion that in those cases there was a practical balance between the two 
antagonistic actions of alcohol upon the digestion. 

Radzikowski experimentally determined that when alcohol is taken into the 
stomach in small amount it increases the secretion of gastric juice, and also its 
contained acid and pepsin. In confirmation of this, Spiro found that an enema 
of from seven to ten C.c. of alcohol causes in man a free secretion of a very acid 
gastric juice in the empty stomach, an effect which is probably due to an excretion 
of alcohol into the stomach, since M. N. Grehant has proven that when alcohol 
is injected into the blood it is excreted into the stomach. Storck finds that the 



202 GENERAL REMEDIES 

digestion of starch within the mouth is increased by the local action of preparations 
of alcohol of the strength of from two to five per cent., but delayed by stronger 
preparations. 

SUMMARY.— Alcohol in large amount is a depressant to the 
cerebral and spinal ganglionic cells, as -well as the nerve-trunks. 
The action of small doses upon the respiratory centres is not thor- 
oughly established, but is probably stimulant ; large doses depress 
the respiratory centres, and finally may cause death by centric 
paralytic asphyxia. Upon the heart the small dose of alcohol 
acts as a direct stimulant, the large dose as a depressant or paraly- 
zant. The influence of minute doses upon the vaso-motor system 
is not thoroughly -worked out, but there appears to be a widen- 
ing of the blood-paths at a time when the heart is still stimu- 
lated, so that there is a marked quickening of the blood-move- 
ment. The toxic dose of alcohol paralyzes the blood-vessels, 
probably both centrally and peripherally. The peripheral temper- 
ature is often increased by small amounts of alcohol, and there 
may be even a slight increase in the central temperature, prob- 
ably caused by quickening of the circulation; the large dose of 
alcohol lowers the animal temperature, probably by causing vaso- 
motor paralysis, and thereby increasing heat-dissipation. 

Alcohol has no specific influence upon the production of heat 
or of carbonic acid, or upon nitrogenous elimination, and, there- 
fore, it has little or no direct effect upon the nutrition, unless it 
be in poisonous doses, when it certainly disturbs all nutritive 
processes. After absorption into the blood, alcohol is to a limited 
extent eliminated through the lungs, the skin, and the kidneys 
unchanged, but is largely, and when in small amount practically 
wholly, burnt up in the system. In its destruction it yields kinetic 
energy which is employed by the organism for its purposes so 
that it (alcohol) is capable to a considerable extent of replacing 
the hydrocarbons of ordinary food, and must be considered to 
have definite food value. 

Therapeutics. — Our knowledge of the physiological properties 
of alcohol shows that its chief therapeutic value in acute disease is 
as a stimulant, a temporary imparter of power which will enable the 
system to stand some strain of short duration, — to bridge over some 
period of weakness. 

The cases to which it is especially adapted may be divided into 
three classes: 

First. — Those in which there is a temporary loss of heart-power, 
as in fainting from exhaustion, loss of blood, or other cause. In 
these cases the alcoholic stimulant should, if possible, be given hot, 
and not much diluted; with it should also be exhibited some more 
rapidly acting diffusible stimulant, such as ammonia. 

Second. — Those acute diseases in which the powers of the system 
are in danger of being used up; to aid in the digestion of food and 
in the maintenance of power. Alcohol, as has already been stated, 
is to a certain extent a food, but it will not of itself sustain life for a 
long time, and should in adynamic disease always, unless for special 
reasons, be combined with milk, or occasionally with eggs. One great 



CARDIAC STIMULANTS 203 

source of its value in these diseases is the power it, imparts of assim- 
ilating food, and in milk punch are furnished the stimulant to di- 
gestion and the most perfect food known for digestion. This use of 
alcohol is apart from its office in the lowest stage of fever as a heart- 
ami nerve-stimulant. Employed for this purpose it is useful in all 
stages of the adynamic fevers, such as typhus and typhoid* By the 
exhibition of three or four ounces of milk every two hours, with one 
or two drachms of brandy or whisky, from the beginning of the 
attack, in many cases the development of the severe adynamic 
symptoms may be prevented. 

A. Oit claims to have experimentally determined upon a fever patient that 
i he value of alcohol as an albumin-saving food is equal to its isodynamic equivalent, 
of a pure food hydrocarbon. 

In the advanced stages of pneumonia, pyemia, exanthematous fever, 
and other acute diseases, when the typhoid state is well developed, 
alcohol should be given boldly, to quiet by stimulation the nervous 
and circulatory systems, to afford a food which will in a measure 
replace the natural pabulum, to aid in the digestion of milk and other 
simple nourishment, to aid in lowering temperature: in a word, to 
enable the system to stand the drain upon its vital powers, and at 
the same time to check such drain. 

Although a great deal of work has been done upon the subject, 
the question as to whether alcohol does or does not, when given 
in moderate dose, increase the resisting power of the system to 
infectious diseases cannot be at pi-esent answered with positiveness. 

Binz found that alcohol increases the resistive power of the dog to septic 
material, but his experiments seem to have been too few to be of value. In an 
incomplete research, H. A. Hare and M. E. Pennington found that alcohol increases 
the bactericidal property of the blood at least against some pathogenic organisms. 
Gruber affirms, as the result of experimentation, that the frequent administration 
of small doses of alcohol to guinea-pigs, infected with bacillus prodigiosus, prolonged 
life, and in some instances even brought about restoration. Opposed to these 
results are those of various investigators. Doyen and Thomas both found that 
alcohol increases the liability of animals to infection with cholera. Abbott, using 
streptococcus pyogenes, bacillus coli, or staphylococcus pyogenes aureus, found 
that the alcoholized animals died with much more certainty than did those of the 
control experiments in which no alcohol was given. Delearde reached the result 
that alcohol destroys the immunization of rabbits against tetanus and anthrax. 
Laitinen, in a very elaborate research upon three hundred and forty-two animals, 
representing six species of mammals and birds, using anthrax, tubercle bacilli, and 
diphtheria toxin, arrived at the conclusion that alcohol diminishes very distinctly 
the resistance of the body towards infectious diseases. Pawlowsky found that 
alcoholized animals reacted much more freely to staphylococcus citreus than did 
the normal animal. Gruber and Koegler determined that alcoholization increases 
the mortality of animals infected with the pneumobacillus. Goldberg came to a 
similar conclusion in regard to the influence of anthrax on pigeons. Ausems found 
that the administration of alcohol in small doses to rabbits before infection 
diminished their resistance. 

* The statement of J. H. Kellogg (Journ. Amer. Med. Assoc, 1895, xxv.), that the adminis- 
tration of brandy markedly lessens the toxicity of the urine in typhoid fever, suggests a very 
important line of research. 



204 GENERAL REMEDIES 

At first sight the experimental evidence which has just been epito- 
mized would seem sufficient to determine that alcohol diminishes 
rather than increases the power of the system to resist various infec- 
tions, and also puts aside immunization. Undoubtedly, however, as 
clearly pointed out by S. J. Meltzer, the doses of alcohol which have 
been used by experimenters have been toxic and not therapeutic, 
so that the importance of the researches is largely invalidated. More- 
over, in most cases the alcohol has been given through the stomach- 
tube, with, as insisted upon by Abbott, resulting erosion and gastric 
inflammation distinctly complicating the bodily condition of the 
animal. 

Properly administered, alcohol always promotes, not arrests, 
secretion in fever cases. The guide to the amount given should be 
the effects produced; so long as the drug lowers temperature and 
pulse-rate, moistens the dry tongue and skin, and quiets the nervous 
disturbance, it does good; if, however, the tongue grows dryer, the 
pulse puts on an angry, bounding character, and the patient becomes 
restless and uneasy, stimulation is being pushed too far, and the 
amount exhibited should be lessened. Whenever the odor of liquor 
appears upon the breath, the patient is almost certainly taking too much. 

The antipyretic action of alcohol has suggested its use in cases of 
high temperature; as, however, this is only one of its actions, and is 
not decided unless very large doses be given, alcohol cannot be em- 
ployed as a general febrifuge. True arterial excitement and sthenic 
inflammation certainly contraindicate its use. The rule may be laid 
down as follows: high temperature is an indication for the use of 
alcohol only when other symptoms also demand it; in itself high 
temperature is never a contraindication to alcohol. In acute sthenic 
diseases, after the progressive stage has passed and the results of the 
disease simply remain to be overcome, alcohol and milk will often 
save life. Thus, in acute pneumonia, when so much consolidation 
has occurred as to render it doubtful whether the exuded matter 
can be removed, or in abscess, when large amounts of pus have formed, 
the demand may be urgent for alcohol as a food and as an aider of 
digestion, and sometimes as a stimulant. 

Third. — Those cases in which there is a depressing agent present. 
In many forms of poisoning alcohol may be used with signal advan- 
tage simply as an arterial and nervous stimulant, to overcome the 
influence of a depressing agent. Thus, when death is threatened 
from cardiac failure in poisoning by toxines, venom, aconite, or simi- 
larly acting toxic agents, whether of animal or of vegetable origin, 
alcohol is an important remedy, unless the poison, as in the case of 
an anesthetic, is physiologically so closely allied to alcohol that the 
small dose of alcohol becomes a reinforcing depressant. In acute 
depression threatening a fatal issue it should be administered freely, 
not much diluted, and, if convenient, hot. From one to four fluid- 
ounces of whisky should be given, repeated every ten or fifteen min- 
utes, until slight intoxication, convalescence, or death has resulted. 



CARDIAC STIMULANTS 205 

What has been said up to this point in regard to the therapeutic 
action of alcohol has had reference to acute disease. The value of 
the drug in some chronic diseases cannot be doubted; hut in prescrib- 
ing it the physician should never lose sight of the possible danger of 
producing a habit far worse in its fruits than is death itself. 

In chronic neuralgia, in hypochondriasis, and in melancholia, 
temporary relief may sometimes be obtained by the use of stimulants; 
but the very relief afforded doubles the temptation to the frequent 
use of the alcohol, and, as the system becomes habituated to its 
action and the dose has to be more and more increased, the habit 
of frequent stimulation grows almost of necessity into drunkenness. 
For this reason we do not think that the physician is ever justified 
in prescribing alcohol for its narcotic stimulant effect in these cases. 
The chief legitimate uses of alcohol in chronic diseases are to aid in 
digestion, to furnish a food which, without any digestive effort upon 
the part of the system, shall be absorbed, and shall take the place of 
more ordinary food, and to check excessive tissue-waste. Of course 
these indications exist only in such diseases as are either dependent 
upon, or closely associated with, a condition of the system in which 
the general nutrition is depraved. In purely local affections the use 
of alcohol is rarely called for except in the last moments of life, when 
it may always be employed to afford relief and to protract for a short 
time the struggle. In chronic dyspepsia, alcohol administered with 
the food often aids very materially in the assimilation of the latter; 
but care should be exercised in prescribing it, for the same reasons 
as were given a moment since when speaking of the use of stimu- 
lants in melancholia. In many cases of chronic neuralgia, not as a 
narcotic stimulant, but as a food and a stimulant to nutrition, alcohol 
is often of service. The danger of establishing a fatal habit in this 
disease is, however, excessive. In almost all cases in which alcohol 
is called for in neuralgia, cod-liver oil is also indicated, and it is 
generally best to exhibit the two remedies together, so as to obtain 
the easy assimilation of the oil and to guard against evil moral results. 

In phthisis, and its congener scrofulosis, while there is room for 
doubt it is probable that the use of alcohol may often prove bene- 
ficial; and in the latter stages of consumption its judicious use as an 
antipyretic narcotic stimulant to lessen the sufferings of the patient 
is perfectly justifiable. During the earlier chronic movements of 
the affection, alcohol taken with cod-liver oil, or in small amounts 
with the food at meal-times, conduces not so much to the 
comfort as to the well-being and recovery of the patient. 

The experience of Arctic explorers has clearly shown that alcohol 
has no heat-producing power, so that at a time when it was believed 
by physiologists to have such influence the Northern navigators had 
learned that the free use of spirits, far from enabling a man to with- 
stand habitual exposure to intense cold, very materially lessened his 
power of resistance. On the other hand, the experience of almost 
every trout-fisherman has satisfied him that spirits do have power 



206 GENERAL REMEDIES 

to prevent, "catching cold" under sudden and unaccustomed expos- 
ure to wet and cold, and that benumbed extremities will become 
warm and have their proper feelings return under the influence of 
a glass of whisky. There is, however, nothing strange or contra- 
dictory in these experiences, and they are both in strict accord with 
our present knowledge of the physiological action of the drug. As is 
often the case, the facts were practically made out, however, before 
science could solve the apparent paradox. It has been abundantly 
shown that alcohol has no heating power; but the chill of sudden 
exposure, the suffering benumbed extremities, the bronchitis that 
perhaps follows, all mean simply this: that, as a result of the cold, 
the blood leaves the surface and the extremities, the circulation fails 
in the outposts, and as a consequence, suppressed perspiration — i.e., 
suspended function of the skin — and internal congestions follow. 
The relief afforded by the spirits, as well as the prevention of sick- 
ness, is due simply to the power of the remedy in maintaining the 
circulation and keeping the external surfaces warmed by the con- 
stantly renewed currents of fresh blood from the interior of the body. 

As an antiseptic alcohol is sufficiently active to be useful on occa- 
sion as a dressing for wounds. Lint soaked and kept constantly wet 
with spirits may be applied. 

Administration. — Almost enough has been already said upon 
this point, but a few further remarks seem appropriate. When 
stimulants are used to sustain the sinking powers in poisoning or 
in disease, the amount given should be almost solely regulated by 
the effects. Thus, in snake-bite it may be necessary to give a pint 
of whisky in the course of an hour; and in low fevers we have seen 
the greatest benefit result, and life apparently saved, by the exhibi- 
tion of a quart of spirits a day. In snake-poisoning, one, two, three, 
or four ounces, as the case may seem to need, should be exhibited 
every ten minutes until some effect is produced or matters become 
hopeless. In low fevers half an ounce to an ounce should be given 
every one, two, or three hours, pro re nata, the practitioner watching 
the results. 

The question of choice, of course, comes up in every case as to 
which of the spirits shall be used. We have never been able to- per- 
ceive any distinct differences in their action (gin, of course, being 
excepted), save only that sometimes one spirit agrees better with the 
stomach than another. This has seemed to us to depend simply upon 
the personal likings of the patient, to which, therefore, the choice 
may well be left. In sudden collapse, some of the wines with a very 
high bouquet are believed to be more stimulating, on account of the 
ethers which they contain. In convalescence, and for habitual use 
in health, wines are preferable to spirits, — more agreeable, more tonic, 
and less likely to lead to excessive indulgence. 

When a mild stimulant is wanted in the beginning of fevers, 
especially if milk punch seems too "heavy," wine tvhey may some- 
times be used with advantage. It is made by pouring a .half^puit 



CARDIAC STIMULANTS 207 

of sherry or madeira into :i pint of boiling milk, stirring thoroughly, 
and, after coagulation has occurred, straining off the whey, which may 
or may not be sweetened, according to the taste of the patient. Mulh d 
wine is often very grateful to patients as a change. It is made by 
beating an egg up thoroughly with three fluidounces of sherry and 
adding a like quantity of water, which must be actually boiling when 
poured in. Champagne is useful in patients with delicate stomachs, 
especially if nausea or vomiting actually exists, and also may be 
employed with advantage in sudden failure of the vital powers, 
especially in elderly persons. It must always be very "dry," — i.e., 
as free as possible from sugar. 

.1////,- punch is prepared by adding from a dessertspoonful to a 
fluidounee of brandy, whisky, or rum, according to the degree of 
stimulation required and the taste of the patient, to three fluidounces 
of milk, with sugar and nutmeg to taste. The addition of a table- 
spoonful of lime-water is not recognized by the palate, and renders 
the beverage more acceptable to the stomach when the latter is weak. 

Eggnog is still more nutritious than milk punch, but is "heavier," 
and is usually rejected by the stomach if given too freely. It is made 
by beating up thoroughly the yolk of an egg with five fluidounces 
of milk and half a fluidounee to one fluidounee of spirits (and half a 
fluidounee of lime-water if required), and adding a sufficiency of sugar, 
with finally the white of the egg previously thoroughly beaten into 
a froth. 

Toxicology. — The acute form of alcoholic poisoning in its 
minor degrees is, unfortunately, an hourly occurrence almost in every 
village, but that fatal results are not absolutely so rare as is generally 
believed is shown by the fact mentioned by Taylor, that in four 
years (1S63-67) thirty-five deaths from this source occurred in Eng- 
land and Wales. It is worthy of note that in some fatal cases con- 
vulsions have preceded death.* The absolute diagnosis of acute 
alcoholic poisoning when the patient is simply seen in the advanced 
stage of deep coma cannot be made out. The odor of liquor upon 
the breath or about the person is simply a proof that the subject 
has been drinking, not that the symptoms are caused by alcohol. 
The manifestations are merely those of profound compression or 
congestion of the brain, of apoplexy, of opium-poisoning; and a man 
whose breath and urine are loaded with alcohol may have been struck 
down with apoplexy or poisoned with opium. Whenever in drunk- 
enness no answer is obtainable by shaking or hallooing at the sub- 
ject, the existence of apoplexy should be strongly suspected, and a 
very careful examination made to detect facial or other palsy; even 
if this be not found, judgment should be suspended. As in apoplexy 
the bodily temperature is frequently elevated, while in acute alco- 
holism it is either normal or subnormal, the existence of fever would 
strongly indicate cerebral hemorrhage. 



See I'. M. 7'., vi. 463. 



208 CENERAL REMEDIES 

A congested ecchymotic condition of the mucous membrane of 
the stomach is the only lesion at all characteristic of an acute 
alcoholic poisoning. 

The treatment is very similar to that of opium-poisoning except 
that in many instances care should be taken to maintain the bodily 
temperature. The stomach should be evacuated, the patient aroused 
by mechanical means, strychnine and digitalis given hypodermically, 
the hot bath employed if necessary, and, finally, if symptoms come 
to the extreme, long-continued artificial respiration (Sylvester or 
forced) should be practised. For the purpose of aiding in the elimi- 
nation of alcohol large quantities of normal saline solution should 
be given by enemata, or preferably by hypodermoclysis. (For case, 
see F. C. Foster, B. M. J., 1903, i.) 

The results of chronic alcoholic poisoning, by their frequency 
and importance, have come practically to rank among diseases, and 
are discussed in treatises upon the practice of medicine, to which the 
reader is referred. 

Methyl Alcohol. — Pyroxylic Spirits. Wood Alcohol. Columbian Spirits. — 
This is a mobile, colorless liquid, of a hot, pungent taste and aromatic odor, highly- 
inflammable, mixing in all proportions with water, ethyl alcohol or ether. It is 
usually obtained by the destructive distillation of wood, and on account of its 
cheapness is largely used in the arts as a solvent. 

Methyl alcohol is capable of producing an intoxication similar to that caused 
by ethyl alcohol, but distinct in the slowness of the onset and the extraordinary 
duration of the symptoms, which may last from three to four days after the com- 
paratively moderate dose of the drug. After distinctly toxic doses the fall of the 
bodily temperature is very marked, and convulsive movements of rhythmic or 
choreic character, followed in a day or two by loss of sensation and reflex move- 
ments are common phenomena. Hemorrhage also frequently occurs from the 
abdominal tract. The eyes are especially affected, nystagmus of a pronounced 
type often being present, also dilatation of the pupil. Chronic methyl-alcohol 
poisoning is far more dangerous than is ordinary alcoholism, and amblyopia due to 
degenerative changes in the ganglion cells of the retina is a very common phenome- 
non. Both in human and experimental poisoning excessive fatty degeneration of the 
liver and other organs is usually found after death. Jelliffe reports multiple neuritis 
following the ingestion of methyl alcohol, and also after inhalation of the fumes. 

Methyl-alcohol amblyopia may appear after a single debauch. It is accom- 
panied with contraction of the fields, absolute, usually central, scotoma, and rapid 
failure of vision; and, though temporary improvement may occur, in ninety per 
cent, of the cases it ends in permanent loss of useful vision. It is worthy of note 
that in many cases methyl-alcohol amblyopia has resulted from the excessive use 
of essence of ginger or peppermint, or other aroma tics, in which the alcohol has 
been used as a menstruum. It has also been caused by the absorption of the alcohol 
through the lungs and skin. It has been shown by A. Birch-Hirschfeld that the 
methyl-alcohol amblyopia is accompanied by demonstrable changes of the retinal 
nerve-cells, and also of the optic nerve. 

The permanency and severity of the symptoms caused by methyl alcohol 
depend in part upon the slowness of its elimination, and in part upon the fact dem- 
onstrated by Reid Hunt, — that it is oxidized in the system with the formation of 
formic acid, a highly poisonous substance. 

Methyl alcohol has been used to some extent in practical medicine, but ap- 
pears to have no other remedial properties than those of ethyl alcohol, and to be 
a much more dangerous remedy. It has very properly fallen into complete 
desuetude as a medicine. 



CARDIAC STIMULANTS 209 

The treatment of methyl-alcohol poisoning is very unsatisfactory. The best 
that can ho done is to aid in the elimination of the alcohol and of the products of 
its destruction within the l>ody by free sweating and by the administration of large 
Quantities of slightly alkalinized water with sodium carbonate.* 

CAFFEINE. 

Caffeine is t he active principle of a large number of plants which 
are used in various parts of the world for the purpose of making 
beverages. Originally discovered in the coffee bean (Coffea arabica), 
it is now manufactured commercially usually from tea leaves (Thea 
sinensis) ; it is also the active ingredient of the kola nut (from Sterculia 
acuminata); of mate (from Ilex paraguensis) of Yaupon or holly 
tea (from Ilex cassine) and of guarana (from Paullinia cupana). 
The last named is the only caffeinic plant recognized by the U. S. 
Pharmacopoeia. 

Guarana is a dried paste, prepared from the seeds of Paullinia cupana, a Brazil- 
ian plant. It occurs in reddish-brown almost sausage-like masses, rugose on the 
surface, very hard, with an irregular fracture and a marbled appearance when 
broken. Its taste is astringent and bitterish; its odor somewhat resembles that of 
chocolate. The alkaloid guaranine, discovered in it by Martius has been shown to 
be identical with caffeine. The U. S. Pharmacopoeia requires that guarana shall 
contain 3.5 per cent, of alkaloids. It has also in it free tannic acid and a fixed oil. 

Caffeine occurs in long, snow-white, silky, opaque, odorless crys- 
tals, sometimes conjoined into feathery crystals, of a feeble bitter 
taste. It has a neutral reaction, but unites with acids to form salts. 
It is soluble, at 77° F., in 45.6 parts of water, 53.2 parts of alcohol, 
three hundred and seventy-five parts of ether, or eight parts of chloro- 
form. It was first discovered in coffee by Runge, in 1820. In 1827 
Oudry discovered a principle in tea which he called theine, which in 
1838 was proved by Mulder and C. Jobst to be identical with caffeine. 
Caffeine is somewhat widely disseminated through the vegetable 
kingdom, but is commercially chiefly obtained from damaged, or 
originally very inferior, tea. 

Official Preparations: 

Fluidextractum Guarana? 1 to 2 fluidrachms (4-8 C.c.). 

Caffeina 1 to 3 grains (0.06-0.2 Gm.). 

Caffeina Citrata (a mixture of equal parts of 

Caffeine and Citric Acid) 2 to 5 grains (0.12-0.3 Gm.). 

Caffeina Citrata Effervescens (2 per cent.) ... 1 drachm (4 Gm.). 
Pulvis Acetanilidi Compositus (10 per cent.) .5 grains (0.3 Gm.). 

Local Action. — Absorption and Elimination. — Caffeine is not irri- 
tant, and for practical purposes may be considered to have no local 
action, except it be upon the sensory nerves. It is absorbed rapidly; 
eliminated chiefly through the kidneys, when in large amount in part 
unchanged, when in small quantity entirely altered (Richard Schnei- 

* See Moulton (J. A. M. A., Nov. 1901); Swan M. Burnett (T. G., Dec. 1901); F. Buller and 
Casey A. Wood (7. A. M. A., Oct. 1904); also Von Graefe (Arch. f. Opth., Bd. lii.; Bd. liv.). 

14 



210 GENERAL REMEDIES 

der, also E. Rost). According to M. Albanese, at least a part of the 
caffeine (trimethylxanthine) appears in the urine as dimethylxan- 
thine, monomethylxanthine, or even xanthine. 

General Action. — The peculiar wakefulness, the increased mental 
activity, and the nervous restlessness which are induced by strong 
coffee are familiar phenomena to almost every one. They are without 
doubt largely, if not altogether, due to the caffeine contained in the 
beverage.* By doses of four or five grains of the alkaloid a somewhat 
similar state of body and mind may be induced. Lehmann found 
that eight grains of caffeine produced increased frequency of the 
pulse, very frequent urination, tremulousness, excited mental action, 
passing into a form of delirium, with confusion of thought, visions, 
and finally a deep sleep. About two hours after taking twelve grains, 
Pratt was seized with intense physical restlessness, conjoined with 
a very uneasy condition of the mind; very marked general muscular 
tremulousness soon followed, and the mental anxiety increased. 
After this state passed off, there was obstinate sleeplessness, with 
active and persistent thinking, and frequent urination. 

According to various observers, the chief symptoms induced by poisonous doses 
of caffeine in the frog are muscular quietness and weakness, with disturbance of 
respiration, succeeded by a stage of violent tetanic convulsions, ending in general 
paralysis and asphyxia, the heart beating after the cessation of respiration, although 
evidently much affected. f 

In birds poisoned with caffeine the symptoms (Brill) are irregular movements, 
apparently to some extent due to cerebral disturbance, increased rapidity and 
irregularity of respiration, spasmodic tremblings, and tetanic and clonic convul- 
sions, with paralytic phenomena. In mammals the results of the toxemia, as noted 
by various observers, are restlessness, hurried respiration, at first a slight lowering 
and afterwards a decided elevation of temperature, muscular weakness, tetanic 
and clonic convulsions, increasing general paresis, and finally death, apparently 
from paralytic arrest of respiration.} 

* The belief that caffeine and theine act dissimilarly upon the normal organization is no longer 
open to difference of opinion. For discussion and literature see p. 317, Eleventh Edition of this 
work. 

Whether the other substances found in the coffee bean play any part in its physiological effects 
is not yet certain. The investigations which have so far been made have been so inharmonious 
as to forbid satisfactory summary, so we dismiss the subject with the following key to the literature: 
Erdmann, (A. E. P. P., 1902, vol. 48); E. T. Reichert (Med. News, 1890, vol. 56); Binz (C. /. M., 
1900, vol. 21); Archangeleski (A. I. P. T., 1900, vol. 7). 

t See Albers (Deutsche Klinik, 1853, 370), Falck and Stuhlmann (Virchow's Archiv, xi. 334), 
Mitscherlich (Der Cacao und die Chocolade, Berlin, 1859), I. Hoppe (L'Echo Med., 1858), Brill 
(Inaug. Diss., Marburg, 1861), Oscar Johannsen (Inaug. Diss., Dorpat, 1869), and others. The 
minimum fatal dose is stated by Leven (Arch, de Physiol., 1858) to be .015 grain in a frog of 
moderate size. 

Johannsen denies the existence of true convulsions in the frog, asserting that there is only a 
rigidity due to an effect upon the muscles. 

Buchheim and Eisenmenger (quoted by Schmiedeberg) corroborate the muscular changes 
noted by Johannsen, but insist that there are also true nervous convulsions. O. Schmiedeberg 
(Archiv fur Exper. Pathol, und Pharm., ii.) believes that he has reconciled these differences of 
observation by finding that the alkaloid acts much more powerfully upon the muscles of liana 
temporaria than upon those of Rana esculenta; so that a dose of caffeine which causes intense 
general muscular stiffness in the former produces in the latter only true convulsions, the convul- 
sions in R. temporaria being prevented or masked by the disorder of the muscles. More recent 
researches (E. Leblond, La Caffeine, Paris, 1883; W. Filehne, Arch. f. Anat. und Physiol., 1886) 
indicate, however, that the differences depend to some extent upon the size of the dose, but in 
still greater degree upon variations in the sensitiveness of individual frogs; thus, Robert (Arch. f. 
Exper. Path. u. Pharm., xv.) found that frogs of the same species are very much more susceptible 
in the spring than in the autumn. The rigidity and paralysis are muscular. 

t In an elaborate series of experiments, Bennett (British Medical Journal, 1874) found that 
the fatal minimum dose of the poison for the cat and the rabbit was a little over a grain for the 
pound, five and a half grains being required for a five-pound animal. 



CARDIAC STIMULANTS 211 

Cerebrum. There is no evidence thai caffeine exerts a very 
marked influence upon the cerebrum of the frog, or even of sonic of 
tl\c lower mammals, unless the convulsions induced by it are believed 

to be partly the result of SO me such action. In certain of the higher 
animals, such as the cat, it often produces a condition of almost 

frantic cerebral excitement. In man the increase of brain-power 
produced by coffee, tea, guarana, and other drugs containing caffeine 
and the allied alkaloids is undoubtedly real, and we must conclude 
that caffeine is a powerful stimulant to the cerebral cortex. It appears 
to us to be our most certain and effective stimulant of the nerve- 
centres connected with the intellectual functions. Those centres 
whose function is consciousness are greatly stimulated, and wake- 
fulness results; while again, in contrast with opium, caffeine increases 
the activity and power of the reasoning faculties at least as much 
as it does that of the imagination. Coffee prepares for the active 
work, both mental and physical, while opium leads its votaries to 
the dream-land of poets. 

Spinal Cord. — There has been much discussion as to the method 
in which caffeine produces convulsions in the frog, but it seems to 
be established that they are, at least in part, of spinal origin. They 
are not prevented by section of the cord high up (Pratt and 
Leblond), therefore they are not cerebral; they are prevented by 
destruction of the spinal cord (Leven), and would appear, therefore, 
to be spinal. 

The difficulty of interpretation of the phenomena has arisen from the fact that 
the muscular action of the alkaloid in a measure masks its influence upon the spinal 
cord, there being both muscular stiffness of purely muscular origin and convulsions 
of spinal origin. This was clearly demonstrated by Pratt, who found that though 
destruction of the lower portion of the spinal cord prevented the convulsions in 
the hind legs of the frog, it did not interfere with the development of the contrac- 
tures. Further, Pratt included all the tissues of a frog, except the spine, in a tight 
ligature just above the bifurcation of the aorta, and administered caffeine, when 
the anterior legs became very stiff, and had also occasional severe convulsions, in 
which the hind legs participated, although between the paroxysms they were 
perfectly relaxed. 

The conclusion seems established that in the frog caffeine acts 
as a motor spinal stimulant and also as a muscle-poison* The physical 
restlessness and tremulousness produced in man by excessive doses 
of coffee and tea, and the convulsions of caffeine-poisoning, are prob- 
ably both spinal and cerebral, though our knowledge of this matter 
is incomplete. f 

Nerves. — The motor nerves appear not to be affected, but the 
sensory nerves are apparently slightly affected. 

* Alexander Bennett has brought forward the theory (loc. cit. and British Medical Journal, 
1874) that caffeine paralyzes the posterior columns of the cord without affecting the anterior 
columns; but his evidence appears to us insufficient to prove his conclusions. He grounds his 
belief chiefly on finding that in poisoned frogs and rabbits galvanization of the posterior columns 
of the exposed cord produced either no muscular contractions or only such as were very much 
more feeble than those provoked by galvanization of the anterior columns. 

t Uspensky (Reichert'i Archiv, lS(i8, 52(1) has found that forced artificial respiration in great 
measure suspends the convulsions. 



212 GENERAL REMEDIES 

Alexander Bennett has found that after death from theine the motor nerves 
retain their normal susceptibility, and Pratt surrounded one crural nerve of a frog 
with a paste "of theine and water," and irritated the spinal cord, when both legs 
responded with uniform alacrity. Bennett also tied the crural artery of a frog, 
poisoned it with the alkaloid, and found that irritation of the cord produced equally 
active contractions in the two legs. The chief evidence as to the sensory nerves is 
furnished by Pratt, who found that when the left sciatic nerve of a frog was sur- 
rounded by a paste of theine and water, after ten minutes irritation of the right foot 
produced reflex movements, while irritation of the left foot failed to elicit any 
response. Leblond has noted marked hyperesthesia in the frog, and Rumpf affirms 
that increased sensibility of the skin can be demonstrated in man. 

Muscle. — The action of caffeine upon the muscle is readily demon- 
strated by throwing the isolated gastrocnemius of the frog into a 
one-per-cent. or even weaker solution; in from two to three minutes 
the muscle becomes markedly contracted, swollen, round, stiff, and 
unable to respond to the galvanic current. That it is the muscle- 
fibre which is affected is shown by the experiments of Pratt, who 
found that when an isolated muscle was soaked in a solution of 
curare until the nerves were killed, and then thrown into a solution 
of caffeine, the usual rigidity was developed. The elaborate studies 
of Leblond appear to prove that there are two stages (as in vera trine- 
poisoning) in the action of caffeine upon the frog muscle, — a primary 
stage, with exaggerated muscular excitability and a tendency to 
prolonged tetanic contractions after momentary stimulation, and a 
final stage of rigidity and lost excitability.* W. Sobieranski believes 
that his ergographic experiments prove that in fatigue caffeine not 
only stimulates the nervous system and thereby increases working 
power, but also acts directly upon the muscle. 

According to the researches of Paschkis and Pal, it would appear 
to be the xanthine which influences the muscle-fibre, since these 
investigators found that caffeine (trimethylxanthine), theobromine 
(dimethylxanthine), and xanthine shared the activity; caffeine being 
the strongest, xanthine the weakest. 

Circulation. — When given in a moderately large dose caffeine 
produces a marked increase in the rate of the pulse with an elevation 
of the blood-pressure. The increase in the pulse-rate is probably 
due to the stimulation of the cardio-accelerator mechanism, while 
the rise of pressure seems to be attributable to a stimulation of both 
the cardiac and arterial muscles. 

According to Voit (quoted by Brill), in the frog the rapidity of the cardiac 
pulsation is at first increased, but the pulsations become slower and slower, and are 
accompanied by irregularity of rhythm, the heart finally ceasing to act, but still 
responding to stimuli at a time when the voluntary muscles are absolutely dead. 
Falk and Stuhlmann, and Johannsen observed that caffeine first increases and 
then lessens the frequency of the cardiac pulsations in the frog. According to 
Johannsen, the lessening of the frequency comes on the more quickly and the more 
powerfully as the size of the dose is increased. After a time the heart begins to 
beat irregularly, with short intermissions, which, as time goes on, grow longer and 

* Johannsen states that when a muscle under the microscope is touched with caffeine its 
fibres can be seen to contract half their length. 



CARDIAC STIMULANTS 213 

longer, till at last movemenl ceases. Johannsen found that the action upon the 
out-out frog's heart was the same upon the viseus in situ; Lebloiul confirms this, 

and stall's that the heart is finally arrested in systole; so also does Thomas J. Mays. 
Aubert and Haase find that the action of the alkaloid upon the pulsations of the 
frog's heart varies greatly; and indeed the individual experiments of the authors 
previously quoted show such variation. This is confirmed by the research of Rios- 
chiro Maki. This investigator experimented upon the cut-out frog's heart with 
the Williams apparatus, and found that the pulse was variously affected. In most 
of his experiments the arterial pressure — i.e., the heart's work — was markedly 
lessened, but in a few cases it was distinctly increased. 

Paul Faval finds that in a proportion of ten centigrammes to one hundred 
and fifty grammes of artificial blood the alkaloid reinforces the isolated frog's 
heart, giving its contractions more amplitude and more energy, but that stronger 
doses depress the heart, and finally arrest it in diastole ; and H. C. Beyer has 
reached similar conclusions with the terrapin's heart. 

Mammal. — The results obtained by various experimenters as to 
the influence of caffeine on the circulation in mammals are in their 
general appearance contradictory, but are, however, we believe, 
reconcilable. 

In attempting such reconciliation it seems better to discuss separately the 
effects of the drug upon arterial pressure and pulse-rate. In the Aubert and Haase 
experiments, caffeine usually produced pronounced fall of the arterial pressure, 
although in one experiment there was a distinct rise. It is to be noted that the 
research was made with enormous doses of caffeine, and usually upon dogs under 
the influence of narcotics. In two experiments upon alcoholized dogs, Binz ob- 
tained a pronounced rise of the arterial pressure; while Maki, experimenting upon 
animals under the influence of atropine or chloral, obtained after large doses a dis- 
tinct fall of the arterial pressure, which in a few cases was preceded by a rise. It 
is evident that the method of research employed in these experiments makes it 
impossible to draw any very positive conclusions. In normal animals, Leven found 
in the first stages of caffeine-poisoning a distinct increase of the arterial pressure, 
and in the elaborate experiments of Reichert it was noted that in the normal dog 
caffeine injected into the jugular vein, in moderate amount, caused a primary fall 
of pressure (evidently due to an overwhelming effect of the concentrated alkaloid 
upon the heart), followed by a rise above the norm, followed in turn, if the dose 
had been large enough, by a marked fall of pressure. Very large doses of caffeine 
produced a persistent fall of pressure, ending in final diastolic arrest of the heart. 
In none of Reichert's experiments was the rise of arterial pressure very great, but, 
except after heavily toxic doses, it occurred almost invariably. Leven asserts that 
after he had divided the pneumogastrics and sym pathetics and isolated the heart 
from all the nerve-centres, caffeine still increased the arterial pressure; while 
Reichert states that not only is the increase of the pressure seen when the animal is 
motionless with curare, but also after destruction of the vaso-motor centres in the 
medulla oblongata. Loewi in oncometrical experiments on the intestines failed 
to obtain any evidences of the contraction of these vessels with caffeine and believes 
that the rise of blood-pressure is purely cardiac. Experimenting on the isolated 
mammal heart, Bock found that though there was a continual increase in the rate 
of the pulse in the majority of the experiments the pressure exerted by the left 
heart was lowered, although in a considerable minority it was first elevated, espe- 
cially when a small dose of the caffdne had been given. Bock concludes from 
these experiments that the elasticity of the heart-muscle is diminished by caffeine, 
and that the elevation of the arterial pressure naturally produced by caffeine in the 
normal animal is due to contraction of the blood-vessels. The method of experi- 
mentation seems to us very uncertain, and the result is in direct discord with other 
experiments already cited. 






214 GENERAL REMEDIES 

The total evidence seems to us conclusively to show that caffeine increases the 
arterial pressure independently of the vaso-motor centres. 

In the advanced stages of caffeine-poisoning both the heart and the vaso-motor 
system are without doubt depressed, so that the cause of the fall of pressure is 
duplex. 

In regard to the pulse, Aubert notes as a constant effect an increase of the 
pulse-rate, and this appears to be the most frequent result produced by caffeine; 
but it has been shown by Reichert that under certain circumstances there is a 
slowing of the pulse. 

Leven asserts that the increase of the pulse-rate is to be seen after isolation of 
the heart from the nervous centres, and is, therefore, due to an action upon the 
heart itself, a conclusion which is in accord with the general results of observat ions 
upon the isolated frog's heart, and is confirmed by Reichert, who believes that 
there are paralyses of the cardio-inhibitory centres, both in the medulla oblongata 
and the heart. The slowing of the pulse occasionally seen in the first stages of the 
poison Reichert attributes, with probable correctness, to a primary stimulation of 
these cardio-inhibitory centres; the alteration of the pulse, which sometimes occurs 
in advanced poisoning he believes to be due to a direct action of the drug upon the 
heart. Bock believes that the frequency of the pulse usually produced by caffeine 
is the outcome of powerful stimulation of the cardiac accelerator apparatus, and 
that the inhibitory apparatus is not depressed, basing the latter belief on the fact 
that he has observed that section of the vagi in the poisoned animal still further 
increases the rapidity of the pulse whose rate is already much above the normal. 

Diuretic Action. — In poisoning by caffeine great increase in the 
secretion of urine is a common symptom, and the statement of Gubler 
that the alkaloid is one of our most powerful and certain diuretics, 
has received abundant confirmation. The effect of the drug upon 
healthy men would indicate that it does not act simply by regulating 
the circulation of the kidney, but has also a distinct effect upon the 
renal organ itself. 

That caffeine acts directly upon the kidneys was proved by W. von Schroder 
and by A. Langgaard, who separately found that when a cannula was inserted into 
the ureters in an animal whose vaso-motor system was completely paralyzed by 
chloral, injections of caffeine into the circulation caused a very great increase in the 
urinary secretion. Langgaard found that usually before the great increase of 
diuresis the urinary secretion was arrested for several minutes. This is in exact 
accord with the experiments of C. D. T. Phillips made with Roy's oncometer. It 
was found that immediately after the injection of a small dose of caffeine, when the 
blood-pressure was either slightly depressed, elevated, or unaffected, the kidney 
underwent a very distinct contraction of its volume, which lasted for two or even 
three minutes and was accompanied by great lessening or arrest of the urinary 
secretion. After the contraction, the kidney rapidly expanded beyond its original 
bulk, and at the same time the urinary secretion became excessive. Loewi found 
that caffeine is capable of dilating the blood-vessels after division of the renal nerves 
and believes that the increased activity of the kidneys depends upon vascular dila- 
tation. These facts do not prove, however, that the diuresis is caused by the in- 
creased flow of blood to the kidneys. It is more probable that the dilatation of the 
vessels is the result, rather than the cause, of the increased secretion. Because the 
secretion from the uninjured kidney was increased much more than from the kid- 
ney whose nerves were destroyed, Schroder believes that the drug increases diuresis 
by acting both upon the nerve-centres and upon the secreting structure of the kid- 
ney. To our thinking, however, the direct injury to the secreting apparatus of the 
kidney by division of the renal nerves is sufficient to account for the difference 
between the influence of the alkaloid upon the normal and the operated-upon kid- 
ney, without necessitating the theory of a twofold action. Schroder found that 



CARDIAC STIMULANTS 215 

there was an increase not only of the liquid, but also of the solids of the mine. Anion 
believes that caffeine increases an inhibitory influence of the pneumogastric nerve 
on the kidney, thereby interfering with its non-oxrret ive influence, a theory which 
seems to us extremely doubtful. 

Temperature. — We know of no recorded temperature-curves of 
caffeine-poisoning in num. It is probable, however, that the effect 
of the alkaloid is precisely what it is in other mammals. Binz states 
thai in animals minute doses have no effect upon the bodily tempera- 
ture; doses just enough to produce slight toxic symptoms cause a 
rise of 0.6° C; excessive doses cause an elevation of 1° to 1.5° C, the 
maximum being reached in one to two hours; doses which rapidly 
kill have very little effect upon the temperature. 

General Nutrition. — The enormous use made by mankind of 
substances containing caffeine indicates that in some way it is directly 
of service in the wear and tear of daily life. The experimental evi- 
dence, however, although not conclusive, does not point towards 
any marked effect of the drug on metabolism. 

This subject was laboriously investigated by Julius Lehmann in 1853, and by 
F. W. Bocker in 1854, and earlier. Lehmann found that the exhibition of six grains 
of caffeine daily, the regulated diet being uniform, diminished the elimination of 
urea from twelve to twenty per cent. Upon experimenting with the empyreumatic 
oil of coffee he found that it lessened even to a proportionately greater extent the 
elimination of urea, and also acted very powerfully in producing sleeplessness, so 
that the favorite beverage is by no means dependent upon its contained caffeine for 
all of its activity. Bocker published his first researches on coffee in 1849, but we 
have never seen any abstract of the article, other than the statement that he found 
that the drug causes diminished elimination of urea. His investigation of the effect 
of tea was most elaborate and laborious. He analyzed the feces, the urine, and 
the products of respiration, and found, a similar diet being maintained, that tea did 
not affect sensibly the elimination of carbonic acid from the lungs, but did very 
decidedly diminish the excretion of urea, and also of nitrogenous matters in the 
feces. He then tried abstaining from food for periods of thirty-six hours, with and 
without the use of tea, with results perfectly in accord with those just stated. The 
results obtained by other experimenters are, however, singularly discordant. Henri 
Hoppe found that, in the dog, coffee diminishes very slightly the urea-elimination, 
but greatly increases the output of carbonic acid. In regard to urea, Rabuteau 
and his pupil Eurastratiade, working with coffee upon men and dogs, obtained 
results similar to those of Bocker, as did also Hammond in this country. On the 
other hand, C. G. Lehmann, Voit, and Roux found that caffeine or coffee sensibly 
increases the elimination of urea, or, in those accustomed to the daily use of coffee, 
has no influence. In a long series of experiments upon dogs by Couty, Guimaraes, 
and Niobey, it is affirmed as a uniform result that the use and assimilation of nitrog- 
enous food were greatly increased, that the carbonic acid and oxygen in the blood 
were markedly decreased, and that the proportion of sugar and of urea in the blood 
was notably increased. 

In the face of so much contradiction it is perhaps wisest to reserve opinion, 
but it does seem as though the present evidences warranted the conclusion reached 
by E. Perisot that the action of caffeine upon urea-elimination and upon protoplas- 
mic change is inconstant, and not direct and pronounced. It is true that in a long 
series of very elaborate calorimetrical experiments performed by E. T. Reichert 
it seems to have been proved that caffeine increases the heat-production as well 
as the heat-dissipation, and that of these phenomena, the increase of the heat- 
production is probably primary. This result is in accord with that of Wilhelm 
Heerlein, who found marked increase in the consumption of oxygen and formation 



216 GENERAL REMEDIES 

of carbonic acid produced under the influence of caffeine. Nevertheless, these 
united results, if their accuracy be accepted, do not show that destructive meta- 
morphosis of nitrogenous tissue is increased by caffeine, but only that there is an 
increased destruction of carbohydrates. 

SUMMARY.— Caffeine is a powerful stimulant to those cells of 
the cerebral cortex "which are functionally connected with con- 
sciousness and intellectual action. It is also mildly stimulating 
to the respiratory centres and probably to the motor cells of 
the spinal cord, but seems to be without action upon the nerve- 
trunks. It is a powerful muscle-poison, at first producing a con- 
dition in which there is exaggerated muscular excitability, with 
a tendency to tetanic contractions upon momentary stimulation, 
and afterwards a stage of stiffness, weakness, and finally, lost 
excitability. It is a mild stimulant to the circulation; probably 
by virtue of its relation to the muscle-fibres it increases the 
cardiac force and perhaps also directly contracts the arterioles. 
In overdose it depresses the circulation, probably acting both 
upon the heart and the blood-vessels. It is absorbed with rapid- 
ity, and is to some extent decomposed in the body, and at least 
in part, eliminated through the kidneys, upon whose secreting 
structure it exerts a marked stimulating influence. Although the 
evidence is contradictory, it is not at present writing probable 
that caffeine has any distinct specific influence upon proto- 
plasmic nutrition, but it does appear to directly increase the 
production of carbonic acid and of a nima l heat. 

Therapeutics. — In accordance with its physiological action, 
caffeine is employed in practical medicine as a cerebral, renal, respira- 
tory and cardiac stimulant. It is often taken to produce wakeful- 
ness and increase the mental power during excessive work. It is a 
valuable remedy for the relief of migraine and other forms of nervous 
headaches, in which its effects are sometimes marvellous, although 
more often it fails to accomplish good. To predict in any case what 
its influence will be, in the present state of our clinical knowledge, 
is impossible; but the remedy may always be tried in safety in the 
dose of five grains, taken when the paroxysm is coming on, and 
repeated in half the quantity once in forty minutes if necessary. It 
is in these cases especially effective in combination with acetphenetidin 
(proportion five grains to fifteen grains) . In opium-poisoning , either 
in the form of unlimited quantities of a strong decoction of coffee 
or of the alkaloid itself, it is a standard remedy, acting by promoting 
wakefulness and stimulating the respiration. 

J. Hughes Bennett found that the exhibition of from four to four and a half 
grains of caffeine would save a proportion of cats poisoned with the previously 
ascertained minimum lethal dose (one and seven-eighths grains) of morphine. Several 
of the cats which had thus been saved succumbed some days afterwards to one 
and seven-eighths grains of morphine. The caffeine was powerless to save animals 
to which larger doses of the narcotic had been given. 

We have had no experience with the use of caffeine as a general 
stimulant in acute adynamia, but various French authors recommend 



CARDIAC STIMULANTS 217 

the remedy very highly, and H. Huchard especially eommends it 
in typhoid fever, asserting that it relieves not only the adynamia, 
lmt also acts as an antipyretic, and through its diuretic influence is 
especially useful when the urine is scanty and albuminous. 

As a circulatory stimulant caffeine is, although a remedy of but 
slight power, at times a valuable adjunct especially in the acute 
forms of circulatory failure. In chronic heart disease it does not 
exorcise any tonic effect on the heart-muscle, indeed it is probable 
that its stimulant action is wasteful of the heart power; so that it 
cannot be compared with digitalis in either degree or kind of action. 

On account of its diuretic action it may frequently be employed, 
with much benefit, in cases of circulatory weakness accompanied 
by dropsy. In chronic Bright' s disease it is often of service, especially 
in the latter stages, when there is marked cardiac failure. In acute 
Bright's disease it should be employed with caution, if at all. It is 
superior to digitalis in never disagreeing with the stomach and in 
having no distinct cumulative tendency. In some cases, however, 
it produces obstinate wakefulness, and we have occasionally found 
it necessary to give it solely in the early part of the day. It is usually 
best to commence with a dose of four grains, given twice daily, 
increased if necessary to twenty or twenty-five grains a day. 

Administration. — For internal administration the citrated 
caffeine is often preferred on account of its solubility. When great 
promptness of action is required, as in cases of sudden collapse or of 
sudden cardiac failure, the hypodermic use of caffeine suggests itself. 
Unfortunately, the ordinary salts are decomposed in the presence of 
water, and are, therefore, ineligible for hypodermic use. The sodium 
and caffeine benzoate has been proposed as moderately stable and free 
from irritating properties. One equivalent of sodium salicylate (160 
parts) will also cause the solution of one equivalent of caffeine (244 
parts), and the following formula has been commended by Tanret 
for hypodermic use: sodium salicylate, thirty-one parts; caffeine, 
forty parts; distilled water, sixty parts. 

Toxicology. — The only case of poisoning by caffeine that 
we have met with is reported by C. H. F. Routh. An adult took a 
drachm of the so-called citrate. The symptoms developed at once; 
they were burning in the throat, giddiness, faintness, nausea, numb- 
ness and tremors of the extremities, pain in the stomach and bowels, 
profuse diuresis, and finally collapse, with cardiac oppression and 
icy extremities. Consciousness was not impaired, and there was no 
headache until the patient began to recover. In a case reported by 
Curschmann, a woman, in order to produce an abortion, took a 
decoction made from about eight ounces of freshly roasted coffee. 
Two hours later she was found in a condition of great anxiety, with 
a sensation of intense need for air; she was exceedingly restless, and 
continually attempted to get up from her chair, but was powerless 
to do so. All the extremities, but especially the hands, were affected 
with very pronounced choreic tremors. She knew persons and her 



218 GENERAL REMEDIES 

surroundings, but her cerebration was very much affected, and the 
next day she remembered nothing that had happened at this time. 
The respiration was quick, 24 and 25 per minute, and short; the 
pulse 112; the heart-beats very strong, even violent. One hour after 
the ingestion of the dose violent diarrhoea set in, and continued until 
the next day. The passages were very thin and watery, with but 
little violent pain, but much tenesmus. There was also marked 
tenesmus of the bladder. The urine was greatly increased in quan- 
tity, with a specific gravity of 1014. P. B. Wing has reported a 
case of amblyopia produced by the excessive use of coffee. 

DIGITALIS. 

Digitalis is the leaves of the Digitalis purpurea,* or foxglove, a 
European perennial plant, largely cultivated for its beautiful purple, 
bell-like flowers. The leaves, which should be collected during the 
second year of the plant's growth at the commencement of flowering, 
are of a dull pale green with a whitish down underneath, from four 
to twelve inches in length and have a bitter nauseous taste and 
faint narcotic odor. 

Our chemical knowledge of the active principles of digitalis is 
far from satisfactory. According to the latest investigations there 
are at least three active glucosides found in the digitalis leaves. These 
are digitalin (of Kiliani), digitoxin and digitonin. The substance 
described by Schmiedeberg under the name digitalein has not received 
general recognition as a pure principle. Digitonin differs markedly in 
its action from the other principles of digitalis and appears to belong 
to the saponin group of principles. It exists in such small quantity in 
the drug as to have very little effect upon the total action of digitalis. 

The term digitalin has been applied to a number of substances. 
Digitalin of the French Pharmacopoeia is generally considered an 
impure form of digitoxin. The substance commonly understood in 
this country by digitalin is the so-called German digitalin (digi- 
talinum Germanicum) ; this is not a pure principle but consists chiefly 
of digitonin and depends for its activity probably upon true digitalin; 
it is asserted also to contain some digitoxin. 

Official Preparations: 

Digitalis 1 to 3 grains (0.06-0.20 Gm.). 

Extractum Digitalis \ grain (0.016 Gm.). 

Fluidextractum Digitalis 1 to 3 minims (0.06-0.20 C.c). 

Tinctura Digitalis (10 per cent.) 5 to 20 minims (0.3-1.3 C.c.). 

Infusum Digitalis (1.5 per cent.) 1 to 4 fluidrachms (4-15 C.c). 

Unofficial Preparations : 

Digitalinum Germanicum \ to \ grain (0.008-0.016 Gm.). 

Digitoxin ^ to T \^ grain (0.3-0.6 Milligm.). 

* The question whether other species of Digitalis have the therapeutic properties of D. pur- 
purea is of great interest. H. Goldenberg (Inaxig. Diss., Dorpat, 1892) states as the results of his 
experiments that D. nervosa, Stend., D. gigantea, Fisch., D. eriostachys, Linn., D. fontanesii, 
Stend., and D. glandulosa all possess more or less of the physiological properties of the official 
species, while D. ferruginea, Linn., is ten times as powerful as the official drug. 



CARDIAC STIMULANTS 219 

Local Action. — Locally, digitalis is probably a Feeble irritant, 
although there is some reason for believing thai the gastric disturb- 
ance which frequently follows the administration of the drug in full 
doses, and which sometimes interferes greatly with its usefulness, 

is at least in part of centric origin. 

Absorption and Elimination.— Digitalis yields its active principles 
to absorption in the intestinal tract with the greatesl slowness and 
with some irregularity, hours usually, and sometimes days, elapsing 
before the full effect of the dose taken by the mouth is produced. 
Even when the drug is given hypodermically the slowness of its 
absorption renders it an unreliable remedy in emergencies. Concern- 
ing the fate of its active principles in the body we have no positive 
knowledge. The experiments of G. IT. Roger indicate that they are 
not destroyed in the liver, and they probably escape from the system 
through the kidneys. 

Physiological Action. — The first evidences of the effect of mod- 
erate doses of digitalis are an increase in the force and a slowness 
in the rate of the pulse, the pulse- wave becoming extremely large 
and hard. If the doses be increased, dicrotism develops, and in- 
creases until the pulse becomes rapid, broken, irregular, and feeble. 
During all this period no symptoms are ordinarily produced; after 
toxic doses, however, there are gastric uneasiness or vomiting, lassi- 
tude, prostration, muscular tremors, lowered reflex activity, and 
sometimes convulsions. (See also Toxicology.) 

Nervous System. — Upon the cerebrum digitalis has no influence; 
indeed, its effects upon the nervous system are everywhere so feeble 
that they are not apparent except after the very largest toxic dose. 

As was first pointed out by A. Weil, digitalis first lessens reflex 
activity by directly — i.e., independently of its action on the circula- 
tion — exciting the inhibitory reflex centres of Setschenow, and after 
a time by directly paralyzing the spinal cord. 

Weil's experiments were in two series. In the first series it was found that 
after small toxic doses of the poison great diminution in the reflex activity of the 
frog was apparent in from ten to twenty minutes, and continued until death of 
the batrachian, but that this diminution for from twenty-five minutes to an hour was 
immediately suspended by section of the cord high up, the reflex activity returning 
at once to its normal state; that after large doses the reflex movements were almost 
abolished in five minutes, and continued so until death, but at any time during 
the first ten or twenty minutes they could at once be ^restored by section of the 
upper cord; and that, both after large and after small toxic doses, a time finally 
came when division of the cord had no power to restore the lost reflex functions. 
These experiments have been confirmed by Meihuizen. In Weil's second series of 
experiments it was proved that the action of digitalis upon the inhibitory reflex 
centres and the cord is direct. In these experiments the hearts of frogs were cut 
out, or their motion arrested by the local application of a concentrated solution of 
potassium nitrate, or rendered slower by a dilute solution of the same salt, and the 
effects of these various procedures upon the reflex activity were studied. It was 
found that slowing of the heart's action did excite the Setschenow's centre, but not 
to nearly so great an extent as did digitalis, and that minute doses of digitalis some- 
times stimulated the Setschenow's ganglion and lowered reflex activity before the 



220 GENERAL REMEDIES 

heart was sensibly affected. In regard to the spinal cord it was proved that when 
the heart was killed by the local action of potash the reflex functions of the spinal 
ganglia remained intact for a much longer period than when digitalis was 
administered. 

Muscles. — That digitalis has some influence upon the voluntary 
muscles has been proved by the researches of Vulpian, of Dybkowsky 
and Pelikan, and of Gourvat, all of whom have found that the muscles 
of frogs poisoned with digitalis respond more freely than is normal 
to galvanic currents. This action upon the voluntary muscles is, 
however, so feeble that according to Gourvat it is distinctly less than 
the influence exerted upon the nerves. There is some reason for 
believing that digitalis affects also the non-striated muscle-fibres 
throughout the body. 

Circulation. — When introduced into the blood stream, in moderate 
doses, digitalis produces a marked slowing of the pulse with a great 
increase in the size of the pulse-wave and a considerable elevation of 
the blood-pressure. After toxic doses the pulse later becomes exceed- 
ingly rapid and irregular, the blood-pressure rises to an extraordinary 
height, which it maintains until the sudden cessation of the heart 
produces an abrupt fall of the pressure. The slowing of the pulse 
is due chiefly to stimulation of the inhibitory mechanism, both 
centrally and peripherally. This inhibitory stimulation, in some 
cases, may be so excessive as to largely counteract the vaso-motor 
effect of the drug, the blood-pressure being in this case but very 
slightly elevated. In the majority of cases, however, the rise of the 
blood-pressure is very marked. This elevation depends in part upon 
the narrowing of the blood-vessels through stimulation of the vaso- 
motor centre, but chiefly upon the increase in the force of the heart. 

If the heart is directly observed (see Fig. 13, page 239) during the 
action of digitalis, the first effect noted is usually the prolongation 
of the period of diastole caused by the stimulation of the inhibitory 
mechanism, but about the same time it can be observed that the 
ventricular systole is more vigorous and complete than normal, so 
that the heart chambers are completely emptied of blood. Follow- 
ing this the ventricular systole becomes not only more forcible, but 
also more prolonged than normal. Sometimes, at this stage of the 
action, the systole is interrupted by an abortive attempt at diastole, 
producing the characteristic dicrotic pulse. In the frog, from this 
stage onwards, the changes in the heart are usually gradually pro- 
gressive. In the mammal, on the other hand, there usually occurs 
an abrupt alteration in the cardiac action; diastole suddenly disap- 
pearing and the pulse becoming extremely rapid. From this time 
onwards till the end of the heart movements, the impulse to con- 
tract constantly encroaches upon the relaxing impulse so that the 
diastole becomes more and more imperfect and the ventricle ap- 
proaches more and more closely to a position of complete permanent 
systole. In the frog's heart this actually occurs; but according to 
our observations the heart of the warm-blooded animals always 



CARDIAC STIMULANTS 



221 




222 GENERAL REMEDIES 

relaxes immediately before complete cessation of movement and 
passes into a stage of fibrillation. Frequently, both in the cold- 
blooded and in the warm-blooded animals, toxic doses of digitalis 
produce a condition sometimes spoken of as delirium cordis, in which 
there is a complete loss of relation between the rhythm of the auricle 
and ventricle. Although Kaufmann brings forward evidence to show 
that the auricles as well as the ventricles are stimulated, yet the 
effect upon the auricles is generally much less than upon the ventricles, 
and frequently, in the frog, the ventricle may be seen in complete 
spasm and the auricle engorged with blood and vainly endeavoring 
to force the fluid into the firmly contracted ventricle. 

The effect of digitalis upon the right heart and upon the pul- 
monary circulation is not definitely determined. The experiments, 
however, of Bradford and Deane, of Popper, and of H. C. Wood, Jr., 
indicate that although the drug has some stimulant action upon the 
lesser circulation it is much less marked than its effect upon the left 
side of the heart. 

The slowing of the pulse produced by digitalis is due to the simul- 
taneous stimulation of the central and peripheral ends of the cardio- 
inhibitory mechanism. In the advanced stage of digitalis-poisoning, 
with the extremely rapid pulse, it has been found that electrical 
irritation of the pneumogastric nerve fails to slow the pulse, showing 
either a paralysis of the peripheral vagi or such a condition of 
irritability of the muscle-fibres that they are unable to respond to 
inhibitory impulses. 

Heart. — It would appear definitely settled that the cardiac phenomena 
produced by digitalis are due, in part, to a direct action upon the heart itself. 

Boehm and Dybkowsky and Pelikan have found that the slowing of the heart's 
beat, the increased energy of contraction, and the irregularity and final systolic 
arrest are produced by digitalis after division of the vagi and destruction of the 
spinal cord. Again, the local application of digitalis at once influences the heart 
(T. Lauder Brunton). Moreover, R. Boehm, using the method of Ludwig and Coats, 
lias determined that in the isolated frog's heart digitalis slows the rate of the beat 
but increases the expenditure of power by the heart. 

After a large dose the condition of cardiac stimulation is followed by a great 
lessening in the output of power, which is apparently due to imperfect diastole 
and consequent non-admission of fluid into the ventricles. The heart is still actually 
putting forth more force, but this energy is wasted in ineffectual spasm, and does 
not accomplish work. The experiments of Williams agree with those of Boehm 
in showing that the cut-out frog's heart actually exerts more than its normal force 
under the influence of digitalis. 

It seems to be clearly established that in poisoning of the mammal by digitalis 
the heart is arrested not in systole but in diastole, since the fact has been confirmed 
by Donaldson and Stevens, by Cushny, and by John P. Arnold and Horatio C. 
Wood, Jr., the latter investigators being well informed of, and meeting Franck's 
denial of the diastolic arrest. The belief of Cushny, that the differences in the final 
result in the digitalized batrachian and mammalian hearts are because the mam- 
malian heart is not capable of continuous systole is confirmed by the experiments 
of Masi, who found that when the frog's heart is warmed to 32° C, digitalis arrests 
it in diastole, and when the heart of the mouse is cooled, digitalis stops it in systole 
instead of diastole; while Donaldson and Stevens have shown that the condition 
of the venous circulation very materially affects the heart-action of frogs. 



CARDIAC STIMULANTS 223 

li <lot^ not seem to us, however, that the whole matter has as yet been worked 
out. Neither the theories advanced l>y Cushny, that the arrhythmia and peculiar 
ventricular movements of the third stage of digitalis-poisoning are the results of 
excessive irritability of the cardiac muscle, and that these and other cardiac phenom- 
ena in the lasi stage of digitalis action are produced by poisons formed in the 
heart itself by its own action, nor the theory that the advanced phenomena of 
digitalis cardiac action arc largely due to excessive stimulation of the accelerators, 
appears to us to be established. In our experiments upon the exposed mammalian 
heart we have seen in the final acts of the digitalis drama happenings so curious 
and unexpected that at present no proposed theory as to the action of the drug is 
sufficient. 

Inhibition. — The cause of the slowing of the heart has been a matter of some 
dispute. Traube stated that, after section of the vagi, digitalis is in warm- 
blooded animals, with rare exceptions, incapable of reducing the pulse-rate, and, 
contrariwise, that when the pulse-frequency has been reduced by the drug, section 
of the nerves causes an immediate and very marked rise in the rate of pulsation. 
King also affirms that section of the vagi completely does away with the slowing 
action of digitalis, and concludes that the lessened pulse-rate is entirely due to 
stimulation of the pneumogastric centres. The bulk of investigators, however, 
"such as Marine, Ackermann, Bulgari, Schnabl, Popper, and Kaufmann" (quoted 
from Cushny), have found that section of the pneumogastric does not completely 
prevent the slowing of the cardiac rate. This would seem to indicate that, in the 
mammal, digitalis stimulates centrally the inhibitory nerve of the heart, while at 
the same time also in some other w r ay it decreases the rate of the cardiac pulsations. 
When to this conclusion is added the fact seemingly established by the separate 
researches of Ackermann, of Arthur R. Cushny, and of Arnold and Wood, Jr., that 
the administration of atropine entirely does away with the slowing of the pulse 
in the mammal, it would appear that this slowing of the pulse is due to a simul- 
taneous stimulation of the pneumogastric centres and of the peripheral inhibitory 
apparatus in the heart. 

It is probable that the comparative effects of digitalis upon the pneumogastric 
centre and periphery differ in different individuals, the centric influence usually 
being the most powerful, but in some cases the nerve-ending being even more sus- 
ceptible to the action of the drug than is the centre; in this way the very pronounced 
reduction in the pulse-rate occasionally produced by digitalis in the mammal after 
section of the pneumogastric may be explained as due to an exceptional sensitive- 
ness of the peripheral ganglia of the individual animals under experimentation. 

In the advanced stages of digitalis-poisoning in the mammal there appears 
to he paralysis of the pneumogastric peripheral ending, or else such exceptional 
irritability of the muscle-fibres that the pneumogastric nerve has lost its control, 
since at this period galvanization of the pneumogastric does not perceptibly affect 
the cardiac action (Cushny, Arnold and Wood, Jr., and others). 

The action on the inhibitory apparatus in the frog seems to be slightly different 
from the effect on the mammal. 

There is no stage in which stimulation of the vagi does not cause diastolic 
arrest. Indeed, Dybkowsky and Pelikan have seen galvanization of nerves produce 
such relaxation in the auricles after the ventricles had already become permanently 
contracted. Further, Boehm has found that a stimulation of the pneumogastrics 
which is insufficient to make itself felt before poisoning will, after the exhibition of 
digitalis, cause diastolic arrest lasting for many minutes. 

The peripheral cardiac inhibitory apparatus shares in the stimulant action of 
digitalis; and as Boehm has found that after section of the vagi diastolic arrest 
never takes place in frogs poisoned with the drug, it is probable that this rare mode 
of death is really due to superexcitation of the cardiac inhibitory nerves. 

On the other hand, however, it does not appear that the condition of inhibitory 
excitement is the sole cause of the slowing of the pulse, since Boehm affirms that 
not only are the partial contractures and the systolic arrest of the heart produced 
in the atropinized frog by digitalis, but also a slowing of the heart-beat. 



224 GENERAL REMEDIES 

The question as to the comparative action of digitalis upon the ventricles and 
the auricles is one of distinct practical bearing, but cannot at this time be fully 
answered, although it is probable that the drug affects the ventricles more than it 
does the auricles. Kaufmann states that he has experimentally proved that the 
diastolic as well as the systolic intra-ventrieular pressure is increased by digitalis, 
but that the diastolic intra-auricular pressure is slightly diminished. This would 
indicate stimulation of the auricles as well as of the ventricles. The pressure within 
the auricles would naturally not be increased, because digitalis does not increase 
the flow of blood from the lungs into the auricle; on the other hand, the intra- 
ventricular pressure during diastole would naturally be increased by any increase 
in the power of the auricle. 

Although digitalis does increase the muscular energy of the heart, it seems 
scarcely possible that the enormous rise of pressure produced by it can be owing 
to this alone. This a priori reasoning has received experimental confirmation from 
Malan (quoted by Fothergill), Fothergill, Gourvat, and Ackermann, who have 
found by microscopic studies that the arterioles of the frog's web, or of the mesen- 
tery of the rabbit, undergo very marked contraction, even to the partial oblitera- 
tion of their lumen, after the exhibition of digitalis. Without attaching too much 
importance to this evidence, the finding of Traube, of Boehm, and of others, that 
after section of the cord high up the arterial pressure is either elevated not at all 
or not nearly so much by digitalis as in the normal animal,* is a strong indication 
that the drug increases the arterial pressure largely by increasing the peripheral 
resistance without centric vaso-motor stimulation. There is, moreover, much still 
weightier evidence of the truth of this conclusion. 

It has been demonstrated by Brunton and Tunnicliffe, that during an inhibitory 
cardiac arrest the blood-pressure sinks much less when digitalis is given than without 
it. Decisive are the independent, though consentaneous researches of Ringer and 
Sainsbury and of Donaldson and Stevens, who, using the method of Gaskell more 
or less modified, have apparently proved that digitalis acts upon the walls of the 
arterioles. They destroyed the nerve-centres of a terrapin, excised the heart, and 
connected bottles in such a way with the blood-vessels that liquids would run through 
the arteries and come out through the veins. Under such circumstances they noted 
a marked reduction of the rate of flow when soluble digitalin was placed in the arti- 
ficial serum. That in the normal mammal, under the influence of digitalis, there is 
pronounced contraction of the blood-vessels seems also to be proven by the experi- 
ments of John C. Hemmeter, made with Ludwig's stromuhr, in which it was found 
that the velocity of the blood-current was markedly decreased by digitalis, though 
the pressure was increased. R. A. Kobertf in a series of experiments similar in 
principle to those of Ringer and Sainsbury, but made upon the excised kidney, 
found that digitalis retards greatly the flow of liquid through the organ, and there- 
fore acts directly upon the coats of the smaller vessels; also that digitalis and the 
nitrites are mutually antagonistic. 

It may be considered as definitely proven that digitalis has a direct action upon 
the walls of the arterioles, but it is highly probable that it also acts upon the vaso- 
motor centre in the medulla. In a series of plethysmographic experiments in which 
digitalin and digitoxin were employed, Gottlieb and Magnus found that the local 
action of digitalis upon the blood-vessels is especially manifested in the region of 
the splanchnic distribution, although contraction even of the volume of the brain 
of the dog was demonstrated as produced by digitoxin. As it is probable that the 
splanchnic nerve almost always dominates the general blood-pressure, a special 
susceptibility to the action of digitalis is not surprising. 

* These experiments have been contradicted bv Ackermann, who states that he has many 
times cut the spinal cord and without exception found a very marked rise of arterial pressure follow 
the injection of digitalis. Unfortunately, none of these experiments have, that we are aware of, 
been published in detail, and it is therefore impossible to analyze or to reconcile them; but Gorz 
(Schmidt's Jahrbiicher, clviii.) expresses the opinion that Ackermann did not fully divide the cord 
in his experiments. Gorz himself found that a rise is produced by digitalin after division of the 
cord, but of so small an amount as readily to be accounted for by the increased power of the heart. 

t Kobert tested two specimens of digitoxin and digitalein which had been supplied by Schmiede- 
berg, their discoverer, and found that instead of contracting the vessels of the kidney they actively 
dilated them and increased the flow of liquid. 



CARDIAC STIMULANTS 225 

Man.- According to our experience, decided therapeutic doses of digitalis, 

in man, produce great reduction of the pulse-rate and sometimes dierofism of the 
pulse, and increase the size and force of the wave, at ilie same time augmenting the 

arterial tension. Poisonous doses induce, after a time, increase of the pulse-rate, 
with Bmallness of the wave. 

Sphygmographic studies of the effect of digitalis upon persons suffering from 
various acute and chronic diseases have been made by Lcgroux, Bordier, Constan- 
tine Paul, and Paul Lorrain. The problems offered by these gentlemen are so com- 
plex as to render a detailed study almost impossible; but, as a whole, their tracings 
seem to confirm our personal experience. Paul Lorrain calls attention to the fact 
that when the drug has reduced the pulse-rate very greatly a second abortive systole 
can. on auscultation, sometimes be heard occurring during the long diastole, and 
some of his sphygmographic tracings are markedly dicrotic. It is evident 
that in man the second systolic movement occurs precisely as in animals; and 
it seems very certain that the proposition framed for the lower mammals applies 
also to man. 

When the pulse has been reduced by digitalis to 40 or 50 a minute, the change 
from the recumbent to the erect position will not infrequently suffice to alter at 
once its character, so that it. will become small and rapid, even 150 per minute. 
The explanation of this seems to be that the heart of such a patient is just in the 
position in which (lie diastolic impulse is being overcome by the excessive systolic 
stimulation of the drug. While the patient is recumbent, the line is not passed 
over, but the additional stimulation of the erect position carries the heart beyond 
the limit of regular diastole, and the over-effects of the drug are at once manifested. 

Urinary Secretion. — The influence of digitalis upon urinary secre- 
tion in health has been studied by numerous observers, with such 
diverse results as to prove that the action of the drug on the kidneys 
is so inconsistent and varying as to render it probable that it is in 
great measure indirect rather than direct. Thus Jorg, Hammond, 
and Brunton have found the secretion more or less decidedly increased, 
and Homolle, Winogradoff, Stadion and, according to Brunton, also 
Krahmer, Kluyskens, Vassal, and Shohl, have found it either 
uninfluenced or diminished. Kaufmann has found it uniformly 
diminished in the dog. 

Investigations made upon the action of digitalis upon the elimi- 
nation of organic matters through the kidneys have yielded such 
contradictory results that at present the conclusion seems justified 
that the drug has no consistent dominant influence upon the output 
either of nitrogenous or inorganic solids through the urine. 

The urea in the apparently very careful experiments of Winogradoff, of Stadion, 
and of Hammond was diminished, while in the almost equally elaborate experi- 
ments of Brunton it was increased. All four observers noted lessening of the chlo- 
rides. Megerand, using the crystallized digitalin of Nativelle, found his urine 
increased twenty-five per cent, but his urea diminished twenty per cent. Auguste 
Meusnier has sought without success for sugar in the urine both of patients taking 
large doses of digitalis and of rabbits poisoned with the drug. Kaufmann states 
that digitalis leaves, or preparations which produce local irritation, cause in the 
dog an increase in the elimination of urea, but that when digitalin was given in 
solution the excretion of urea was diminished. G. P. Sereschnikow, as the result 
of experiments upon man, finds that digitalis has no pronounced constant effect 
upon nitrogenous elimination. He is confirmed by Alexeevsky, while I. Beljikow 
assorts that the drug increases the elimination of the chlorides, sulphates, and 
phosphates. . . 

15 



226 GENERAL REMEDIES 

Temperature. — Toxic doses of digitalis lower the temperature a 
number of degrees in healthy men and animals. It would seem, 
however, that the fall of temperature is generally, if not always, 
preceded by a rise, as has been noted by Bouley and Reynal, by 
Dumeril, Demarquay, and Lecointe (quoted by Brunton), by Hirtz, 
by Legros, and by Gourvat. Kaufmann believes that such rise is 
due to the local irritation caused by the drug, and asserts that if no 
irritation be produced there is always in the animal a fall of rectal 
temperature (0.4°-0.5° C.) after even a feeble dose of digitalin. 

The effect of therapeutic doses in the normal condition has not 
been closely studied, that we are aware of. But in a number of cases, 
chiefly of pneumonia, Z. E. Coblentz found that about twelve hours 
after the fall of the pulse there was also a fall of temperature. The 
tendency of our present knowledge is to connect the changes in 
temperature induced by digitalis with the changes of the circulation; 
and it seems very possible that therapeutic doses in health may be 
found to increase bodily heat, although in fever they may diminish it. 

SUMMARY. — It would appear to follow, from experiments upon 
frogs, that the toxic dose of digitalis primarily inhibits reflex 
action by stimulation of Setschenow's centre, and subsequently 
directly paralyzes the motor tract of the spinal cord. This in- 
fluence is not, however, very apparent, even in the lower mam- 
mals, and in the human individual the symptoms of digitalis- 
poisoning' are chiefly manifested in irritation of the stomach and 
disturbance of the circulation, death finally occurring in collapse, 
sometimes preceded by delirium, stupor, or convulsions, though 
consciousness is long preserved. The therapeutic dose of digitalis 
acts almost solely upon the circulation, slowing the rate and in- 
creasing the force of the heart's beat by a direct stimulating 
action on the pneumogastric nerves and upon the heart itself. 
By this cardiac influence, and also by contracting the blood-ves- 
sels through a direct action upon their walls, and also probably 
upon the vaso-motor centres, the therapeutic dose of digitalis 
enormously increases arterial pressure. Probably by its direct 
influence upon the heart-muscle, and also by stimulating the 
pneumogastric or trophic cardiac nerve, and by increasing the 
blood-supply of the heart, in certain diseased conditions digitalis 
acts not only as a cardiac stimulant, but also as a cardiac 
tonic. In the frog the heart stops in systolic spasm; the mam- 
malian heart, after going into a condition of fibrillary contrac- 
tions, ceases all movement in diastole. The active principles of 
digitalis are absorbed and probably eliminated through the kid- 
neys, though in health the diuretic action of the drug is ex- 
tremely uncertain. Upon the alimentary canal digitalis acts as 
an irritant, affecting the stomach more than the intestines, and 
often, when in full dose, producing gastric pain and vomiting. 

Therapeutics. — The chief clinical use of digitalis is in diseases 
of the heart; and from what has been said of its physiological action 
it logically follows that it should be useful in loss of cardiac power. 






CARDIAC STIMULANTS 227 

When the muscle of t he heart is for any reason unequal to the 
task set it, the systoles become rapid and imperfect, and by this 
irregular action, the ventricles neither completely filling nor com- 
pletely emptying themselves, increase the embarrassment. Under 
these circumstances, digitalis, by lengthening the diastolic pauses 
and increasing the force of the systolic contractions, causes the ven- 
tricles to fill themselves completely in the one and to empty them- 
selves completely in the other act. By subduing irregular action 
through the inhibitory nerves, and by energizing the muscular power 
of the heart-walls, the remedy is of incalculable service, and, increas- 
ing arterial tension all over the body, causes the disappearance or 
lessening of symptoms due to low pressure in the arteries. 

It is a logical necessity, if our reasoning as to the physiological 
action of digitalis has led to a correct result, that the drug should be 
of the greatest service when the lesion is simply loss of cardiac power; 
and clinical experience tallies with this a priori argument. In simple 
dilatation, or in simple failure of the cardiac muscle without degenera- 
tive changes or valvular lesion, the results of the use of digitalis are 
most favorable. 

On the other hand, in simple hypertrophy digitalis does harm, 
and should never be used. It must be borne in mind that although 
this agrees with what the experimentalist has proved to be the action 
of digitalis, yet it was discovered independently as a clinical fact by 
practitioners. Thus, Niemeyer, — who ridiculed experimental thera- 
peutics because he would not take the trouble to study it deeply 
and practically and was therefore incapable of understanding it, — 
says, "'Digitalis in pure uncomplicated hypertrophy is unsuitable." 

Valvular lesion of the heart, as is well known, gives rise under 
unfavorable circumstances to dilatation, but in favorable cases to 
hypertrophy, or rather in the great majority of cases to hypertrophy 
with dilatation. Following out the principles already inculcated, it 
might seem at first that the use of digitalis in hypertrophied hearts 
with valvular lesion ought to be reprobated. But it is known clini- 
cally that digitalis often does good in valvular lesion with enlarge- 
ment of the heart. The results of logical deductions from our physio- 
logical conclusions as premises are, however, not really at variance 
with this. It must be borne in mind that structural hypertrophy 
and functional hypertrophy are different things: by this is meant 
that although a heart be enlarged and absolutely stronger than 
normal, yet it may be, relatively to the work required of it, weak. 
Thus, if 1 represents the normal work of the heart and 1 its normal 
power, if the former be increased to 4 and the latter to 3 the heart 
is really in the position of a weak organ, although possessed of three 
times its original strength. Hence it is that digitalis is often useful 
in valvular disease with hypertrophy. In the vast majority of cases 
the heart with diseased valves is in the position just spoken of; but 
sometimes the work advances only to 2 and the strength to 3; then 
the hypertrophy being excessive, digitalis increases the difficulty. 



228 GENERAL REMEDIES 

In mitral insufficiency and in mitral stenosis digitalis is often of 
great service. It is evident that in both instances the valvular lesion 
leads as its first result to pulmonic hyperemia. How does the digitalis 
lessen this? In the case of stenosis, the diastole being lengthened 
by the remedy, the auricle is afforded more time to empty itself into 
the ventricle through the narrowed orifice, and at the same time is 
strengthened in its contracting power; evidently, then, the left 
ventricle when its systole occurs will have much more to contract 
on than before the digitalis was administered, and the amount of 
blood in the systemic circulation will be increased, — i.e., the amount 
in the pulmonic circulation will be diminished; further, the right 
ventricle will have greater power afforded it to force the blood through 
the lungs. 

In mitral insufficiency the mechanism is different, but the result 
is the same. The increased power of the systole will throw propor- 
tionately more blood through the aortic orifice than through the 
partially open valve. The opening at the insufficient mitral valve 
is much smaller and more obstructed than the aortic orifice. As the 
force or rapidity of the current increases under the action of digitalis, 
the friction becomes greater at both orifices, but the ratio of increase 
is evidently far higher in the small choked mitral leak than in the 
wide aortic opening. Hence the large orifice constantly gains upon 
the smaller as the cardiac force is increased, and more blood passing 
into the systemic circulation, the pulmonic vessels are relieved. 
Again, the right ventricle shares the stimulant action of the drug, 
and acts more strongly upon the pulmonic circulation, resisting the 
direct backward flow from the auricle. There are cases of mitral 
cardiac disease in which digitalis seems to be indicated, but when 
given acts unhappily. In some of these cases the augmented distress 
is probably caused by a strain upon the auricles. If the ventricle be 
already too strong for the auricle, and if by virtue of a very patulous 
mitral valve the backing of the blood upon the auricle is very easy, 
it is readily understood how increasing the power of the ventricle 
may augment the auricular strain. Especially is this consideration 
important in the light of Kaufmann's researches, which seem to show 
that the ventricle is more affected by digitalis than is the auricle, 
and hence that a stimulated ventricle may have to be met by a 
non-stimulated auricle. 

In aortic constriction digitalis is useful when the heart-power 
begins to fail. In these cases compensatory hypertrophy, with slow- 
ness of action, is very apt to occur, or even to become excessive; 
much more frequently does this happen than in mitral disease. Again, 
in aortic insufficiency the prolonged diastole of digitalis action favors 
the return of blood to the heart, and is not advantageous. It is evi- 
dent that digitalis is not so generally useful in aortic as in mitral 
disease: nevertheless, when the heart- muscle fails, and the hyper- 
trophy is not compensatory, the drug is useful in both aortic stenosis 
and insufficiency. . 



CARDIAC STIMULANTS 220 

From the considerations which have been brought forward, it 
is very evident that a knowledge of the relation of the heart-muscle 
to the work required of it in any individual case is much more 
necessary to the therapeutist than to know what valve is diseased. 

In "irritable heart" of soldiers — a disease or condition of cardiac 
irritability evidently connected with muscular weakness, and very 
probably dependent upon exhaustion of the inhibitory nerves — Da 
Costa Found that in the early stages of the affection digitalis not only 
acted better than any other remedy, but even, when administered 
continuously for some time, often effected a permanent cure. When 
hypertrophy had taken place, the drug was of little use. 

The relief afforded by digitalis in not too inveterate cardiac disease 
is often in a measure permanent, because the drug may aid very 
materially in the production of compensatory hypertrophy. Dilata- 
tion is certainly more likely to occur when the muscular fibre is lax 
and acting feebly than when it is toned up and in vigorous play; 
secondly, the stimulus to action in a muscle is almost of necessity 
directly or indirectly a stimulus to its nutrition; thirdly, it appears 
probable from the researches of Gaskell that the period of inhibition 
is one of structural upbuilding, and that therefore the pneumogastric 
nerve is trophic in its nature, so that it is probable that digitalis, 
by stimulating the trophic cardiac nerve, benefits the cardiac nutri- 
tion. Lastly, improved systemic circulation means in a far more 
intense degree improved blood-supply to the cardiac muscle, because 
the coronary arteries being comparatively small vessels springing 
almost at right angles from the aorta, the tendency of the blood 
is to flow onwards; consequently a considerable degree of pres- 
sure in the aorta as well as resistance in the peripheral vessels 
is necessary for the proper filling of the coronary circulation and 
nutrition of the heart. These conditions are peculiarly favored by 
the big slow pulse of digitalis and by the vascular constriction. 

That digitalis exerts the nutrient and trophic influence here set 
forth has been strongly confirmed by the research of Hare and Coplin, 
in which it was found that the continuous giving of digitalis to young 
pigs produced a distinct increase in the size and weight of the heart 
as contrasted with control animals of the same litter. 

If in aneurism, or in general capillary atheroma, there be increased 
resistance to the circulation, and the heart have not sufficient power 
to meet this, digitalis may be useful, but must be employed with 
caution. It not only increases arterial pressure, but also causes the 
pulse-wave to be of enormous size as well as power, so that there is 
great danger of distending and tearing open the thinned wall of an 
aortic aneurism. The use of digitalis for the purpose of "quieting 
the circulation" in aneurism is very dangerous. We have seen 
immediately fatal hemorrhage produced thereby. 

In cardiac dropsy digitalis is of service probably not only by 
regulating through the heart the circulation, and by evacuating the 
surplus fluid through the kidneys, but also by an action upon the 



230 GENERAL REMEDIES 

vessels, vaso-motor weakness being evidently a strong factor in the 
production of dropsy. 

In endocarditis and in myocarditis with marked irregularity of the 
cardiac action and failing power there is naturally a strong impulse 
to the administration of digitalis. It should be remembered, how- 
ever, that in an acute inflammation of the lining membrane of the heart 
the action of the heart is often really of the nature of an excitement, 
and that therefore, it would a priori be expected that digitalis would 
do harm rather than good. Restrained by this belief, we have never 
used digitalis boldly in this condition, but from the doses given have 
failed to perceive any good effect. In the after-stages of an endo- 
carditis, when the heart is troubled with recent patency of valve, 
digitalis is a remedy of the very greatest importance, often relieving 
the symptoms distinctly and very strongly favoring the development 
of that compensatory hypertrophy in which lies the only hope of the 
patient. During the exhibition of the digitalis, however, the patient 
should be closely watched, and any evidence either of overaction of 
the drug or of overgrowth of the heart should lead to the suspension 
of the remedy. 

In acute myocarditis digitalis is commonly absolutely inefficient. 
How far its action upon the muscle itself will render it harmful is at 
present unknown. 

These statements are so correct that in cases of rapid degenera- 
tion of the muscles from diseases of the coronary artery the effect of 
digitalis can sometimes be made available for diagnostic purposes. 
When the symptoms point strongly to coronary artery diseases, and 
digitalis freely given fails to exert any perceptible nfluence upon 
the heart, the prognosis is most grave. 

Digitalis in large doses is a valuable cardiac stimulant in syncope 
or sudden collapse from hemorrhage or other cause. To overcome 
its slowness of action we have used it hypodermically often with 
excellent effects. From twenty to thirty minims (1.3-1.8 C.c.) of 
the tincture should be injected into the arm, and repeated in half 
an hour if absolutely necessary, or a grain (0.06 Gm.) of digitalin 
may be substituted. In these conditions, however, strophanthin is 
probably better, because more prompt. 

In many cases of general debility or so-called neurasthenia, al- 
though there may be no disease of the organs especially concerned 
in the circulation, the latter is exceedingly feeble and, as a conse- 
quence, all portions of the system are imperfectly supplied with blood. 
Under these circumstances preparations of digitalis are very useful 
as general tonics. 

A number of eminent physicians assert that they have obtained 
excellent results by the use of half an ounce of the tincture of digitalis 
in the treatment of delirium tremens, especially in those cases in which 
the pulse is very soft and feeble. The evidence of the value and 
safety of the remedy in such cases is too strong to be overlooked, 
but does not indicate the possession of narcotic properties by the 



CARDIAC STIMULANTS 231 

drug. The rest and sleep which have followed the administration 
have probably been the resull of the cardiac stimulation and the 
increased Bow of blood to bhe nerve-centres. Enormous doses of 
digitalis are tolerated in these cases, probably because the heart 
has become by long habit very much benumbed to the influence of 
stimulants. Their use is not, however, entirely free from danger. 

Digitalis is a very important remedy in the treatment of poison- 
ing by such substances as muscarine, delphinine, aconite, and the 
nitrites, which have been proved to be directly antagonistic to it in 
their action upon the heart. 

Dobie reports a ease of recovery after the ingestion of an ounce of Fleming's 
tincture of aconite, apparently due to the hypodermic injection of twenty minims 
of tincture of digitalis and the exhibition by the mouth of three doses in an hour of 
a mixture of tincture of digitalis (one drachm each dose), brandy, and ammonia. 

Digitalis is often of great value in various acute diseases,* such as 
adynamic pneumonia and adynamic fevers, by maintaining the heart's 
action. It can have no effect upon the diseases themselves, but may 
help most opportunely to sustain the heart during a crisis or a period 
of strain upon it. When in any form of pneumonia^ the right heart 
is yielding to the strain of forcing blood through pulmonic capillaries 
pressed upon and reduced in their aggregate lumen by exudation, 
digitalis may be of service. 

With the idea that digitalis is an active antipyretic, it has been 
prescribed in various acute diseases, sometimes with asserted good 
results. There seems to be no good physiological basis for the anti- 
pyretic use of digitalis; but some clinical evidence in favor of such 
action is furnished by the records of Wunderlich, according to which 
from half a drachm to a drachm of digitalis, given in divided dose 
during three or four days in the second or third week of severe typhoid 
fever, immediately produced a slight fall of temperature in a large 
proportion of the cases, and sometimes a considerable fall. Far more 
extensive and complete observations must be made upon a rising, 
not a falling temperature before any satisfactory conclusion can be 
reached. At present the antipyretic use of digitalis should be purely 
tentative. In puerperal fever Winkel believes that digitalis does good 
by its action on the heart, by contracting the arterioles of the uterus, 
and by lowering temperature. 

The property of causing contraction of all unstriped muscular 
fibres has been attributed to digitalis, but, while the probabilities 
are certainly such as to invite investigation, we have no definite 
knowledge upon the subject. Dickenson asserts that it has a power- 
ful action in causing the uterus to contract and to arrest hemorrhage, 
— in menorrhagia, a few minutes after an ounce and a half of the 

* Consult Hankel (British and Foreign M edico-Chirurgical Review, xxxi. 513), Grimshaw 
(Dublin Quarterly, June, 1873), and Anstie (London Practitioner, September, 1873). 

t According to the experiments of F. Badano (A. I . B.) the normal toxicity of blood-serum 
and of urine diminishes very greatly in pneumonia, but is in large measure restored under the 
action of digitalis. 



232 GENERAL REMEDIES 

infusion is swallowed, severe pains resembling those of the first stage 
of labor coming on, with a momentary profuse discharge of blood 
and clots, if there be any present, followed by arrest of the flow for 
hours. Stadion states that digitalis is capable of temporarily but 
completely annulling the activity of the sexual organs, and that it 
may be regarded as a true anaphrodisiac. M. Gaunot makes the same 
assertion, and advises the use of the drug in spermatorrhoea. 

Toxicology. — In poisoning by digitalis, the first symptom of 
any severity is generally vomiting of mucus and bile, very violent 
and very often repeated. At the same time a feeling of heat of the 
head, disordered vision, and vertigo manifest themselves. The pulse 
at this time in the horizontal position may be full and strong and slow, 
but on the patient's rising becomes weak and rapid. The face is pale. 
The vomiting continuing, profound prostration comes on, and the 
pulse becomes feeble, small, and irregular, although the beat of the 
heart may be strong and hard. The eyes are very prominent, the 
pupils fixed and dilated; * according to Tardieu, an almost diagnostic 
symptom is the blue color of the sclerotic. Abundant salivation 
sometimes occurs. Intense headache and pains in the back or limbs 
are often complained of. Diarrhoea is very generally present; the 
urine may be suppressed. The intelligence is often perfect in the 
midst of profound collapse, but delirium more or less violent finally 
comes on. Death, usually preceded by stupor or by convulsions, 
takes place most frequently in one or two days, but has occurred as 
late as the tenth day and as early as three-quarters of an hour.| 

H. O. Hall, in accordance with the previous statements of Doro- 
ziez and other French writers, states that when given only in full 
medicinal doses digitalis may produce hallucinations and even 
violent delirium. Such results must, however, be an extremely 
rare phenomenon. 

In the majority of cases of digitalis-poisoning the patient recovers. 
When this happens, the symptoms gradually ameliorate. Cardiac 
weakness, and even a bruit de souffle, with more or less exophthal- 
mos,! are sa id to have persisted for weeks in some cases. In poison- 
ing by digitalin the symptoms are those of rapid digitalis-poisoning, — 
violent vomiting, intense cephalalgia, and sometimes rachialgia, 
irregular, feeble, intermittent pulse, and paroxysms of suffocation. 

The minimum fatal dose of digitalis is not known. 

A large teaspoonful of the tincture is said to have caused alarming symptoms 
in a young puerperal woman (Tardieu); twenty grains of the extract proved fatal 
on the tenth day (Tardieu), and two and a half grammes of the leaves in infusion 
on the fifth day (Tardieu); fifty granules (one-fiftieth of a grain each?) of digitalin 
have been recovered from (Tardieu); about one-fourth of a grain of digitalin pro- 

* Hauber {Munch. Med. Wochensch., 1890) details a case of death, due, according to his belief, 
to digitalis-poisoning, with contraction of the pupils. 

t See case reported by M. Barth (quoted by Tardieu). In a case of poisoning by ten grammes 
of tincture of digitalis, said to contain twenty milligrammes of digitalin, the symptoms were vomit- 
ing, great pain in the head, prostration, a very small pulse, — 40 per minute, — anuria, and a systolic 
bruit heard over the whole heart, having its maximum intensity at the base. Recovery occurred 
in two days (Mem. Soc. de Med. de Bordeaux, 1884, 397). 

% G. H. M. C, July, 1874. 



CARDIAC STIMULANTS 233 

duoed very violent but not lethal symptoms. In the only fatal ease of digitalin- 
poisoning we know of {Affaire Couty de la Pomerrais), the amount ingested was 
unknown, in a case reported by Frank Radcliffe, one-twentieth of a grain of Nati- 
oelle's digitalin is said to have caused vomiting, profuse sweating, feeble, irregular, 
intermittent pulse, shallow and slow respirations, coma., ending in recovery. 

The treatment after the evacuation of the stomach and bowels, 
and the very free administration of tannic acid (as the best, although 
unreliable, chemical antidote) — should consist in the exhibition of 
opium, strychnine, and alcoholic .stimulants, with rest in the hori- 
zontal position. We know of no recorded experiences with the 
antagonistic poisons to digitalis, such as aconite or muscarine. 

lv Zugsmith reports a case of violent cumulative action of digitalis in an infant, 
in which, acting upon the theory that fever overcomes the cardiac influence of 
digitalis, he exposed the child to high temperature in a vapor bath at 120° P., with 
immediate relief of the symptoms. After sixty hours the symptoms had sufficiently 
disappeared to allow the removal of the child from the bath. 

Two cases, one ending fatally, of what may be considered chronic 
digitalis-poisoning have been reported by Kohnhorn. The symptoms 
were loss of appetite, tinnitus aurium, vertigo, lowering of the rate 
and force of the pulse, diarrhoea, weakness, general anemia, and 
syncopal attacks. The only lesion found at the autopsy was con- 
gestion with ecchymosis of the gastro-intestinal mucous membrane. 

Administration. — Digitalis may be given in emergencies where 
single doses are administered, in much larger quantities than those 
given as the usual doses. Thus, of the tincture, two fluidrachms 
or even half a fluidounce may be exhibited; of the infusion, a wine- 
glassful. Moreover, in desperate cases, the physician is justified in 
taking the risk of the administration of repeated very large doses of 
digitalis. We have seen a number of cases of excessively severe 
chronic cardiac failure, with Cheyne-Stokes respiration, orthopncea, 
and almost absolute insomnia, in which the administration of half a 
fluidrachm or a fluidrachm of the tincture of digitalis three or four 
times a day has enabled the patient to resume for a time the ordi- 
nary duties of life. In almost every case of this character, which we 
have watched, death has finally come by sudden syncope, while the 
patient was still going about and enjoying a comfortable life. We 
do not believe that the arrest of the cardiac action has been due to 
a direct action of the drug, but to the fact that the enormous doses 
have stimulated the heart and steadied its expenditure of force, so 
that it was enabled to go on until the last particle of cardiac vital 
power was exhausted. H. C. Wood further says that in an experience 
of forty-four years in which he has used digitalis, frequently in enor- 
mous doses, he has seen but one case in which he thought it did serious 
harm by a toxic action. The infusion of digitalis is believed by many 
practitioners to be more active than the tincture. This is simply 
because the infusion is commonly used in much larger doses than the 
tincture. Either preparation is efficient if properly made from fresh 
leaves. 



234 GENERAL REMEDIES 

When digitalis is administered persistently, its first evident in- 
fluence may be suddenly developed after long delay. It is said that 
sometimes the first marked symptom of this so-called "cumulative 
action" is severe syncope, followed by paraplegia, vomiting, diar- 
rhoea, delirium, general insensibility, and death. Such cases must 
be extremely rare: usually a sudden drop of the pulse is the most 
serious effect, provided that the administration of the remedy be at 
once suspended. It is a matter of much importance to determine 
when this cumulative action is to be expected. It is probably con- 
nected with slow absorption and elimination, and is much more 
prone to occur when there is no diuretic effect. It is also very likely 
to appear after tapping: the sudden removal of pressure from the 
vessels leads to the picking up from the tissues of serum, — saturated, 
it may be, with digitalis principles, — and also to the rapid absorption 
of any digitalis which may be in the alimentary canal. 

In a very elaborate, careful research, Fraenkel has found that digitalis gluco- 
sides have, when given continuously to the lower animals, a very distinct tendency 
to cumulative action, and to a sudden passage of the therapeutic over into the toxic 
effect. The tendency of this influence was much greater with digitoxin than with 
digitalinum verum; indeed, Fraenkel found it very difficult to experimentally produce 
marked, continued slowing of the pulse with digitoxin without causing fatal poison- 
ing. For the reason that Heide and also Stokvis liave shown that the very soluble 
helleborein, and because he himself has determined that soluble strophanthin has a 
marked tendency to cumulative action, Fraenkel believes that this action is due to 
such permanence of union between the glucosides and the heart tissue that the 
muscle refuses to give up the glucoside to the process of elimination, and continually 
adds the new doses to itself. 

In the experiments of Fraenkel, digitoxin was found to be an extremely danger- 
ous remedy in the lower animals. It was also made out that 0.08 milligramme 
was the toxic equivalent of 0.48 of digitalinum verum; so that, as far as physio- 
logical experimentation goes, digitalinum verum was found to be much safer and 
much more prompt in its action than digitoxin. 

T. Lauder Brunton and J. Theodore Cash find that high tempera- 
ture so affects the cardiac inhibitory apparatus in the cat that it 
will not respond to digitalis, and believe that high temperature 
greatly interferes with the action of digitalis. In this they are abun- 
dantly sustained by general clinical experience; very commonly in 
high fever it seems almost impossible to obtain the digitalis pulse.* 
In pneumonia and other diseases with high temperature and a sudden 
defervescence some care should be exercised in the very bold use 
of the remedy, lest when the temperature suddenly falls inordinate 
digitalis effects may appear. Fear of the cumulative action of 
digitalis should not interfere with its persistent administration in 
cases of cardiac or other disease in which it is indicated, but should 
lead the practitioner to interrupt its use at intervals so as to allow 

* It is probable that all active poisons are greatly influenced by high temperature. It is said 
that in order to cause the death of dogs suffering from septic fever, fifteen to thirty per cent, beyond 
the ordinary fatal dose of the following poisons is required: strychnine, curare, morphine, atropine, 
nicotine, veratrine, digitalin, helleborein, chloral, formaldehyde, sodium nitrite, cobalt, nickel 
chloride, iron chloride. (See Arch, di Farmacol. e Terap., viii. 1900.) 



CARDIAC STIMULANTS 235 

the clearance of the system. For ordinary cases the official prepara- 
tions are preferable to any so-called "active principle" or secret 
preparation. Indeed Kakowski failed to obtain the same stimulant 
effect on the isolated heart, which he obtained from the tincture or 
infusion, with either digitalein, digitalin or digitoxin. 

If a representative of digitalis in small bulk be desired, probably 
the best preparation is Merck's digitalinum Germanicum.* This 
preparation has been deemed uncertain, but according to the clinical 
reports of Beates and the experiments of Arnold and Wood, this is 
because it has been habitually given in absurdly small dose. Ac- 
cording to the closely agreeing results of these investigators, one- 
quarter of a grain (0.016 Gm.) is about equivalent to fifteen minims 
(1 C.c.) of the tincture, and represents the full therapeutic value of 
digitalis. 

Digitoxin, according to the experiments of J. P. Arnold and H. 
C. Wood, Jr., of Zeltner, and of Curioni, affects the circulation of the 
lower animals as does digitalis. The tendency of it to act cumula- 
tively, so marked in the experiments made by Fraenkel, has been 
confirmed by Arnold and H. C. Wood, Jr., and clinically by Zeltner. 
Digitoxin is locally very irritant, and is probably at least as prone 
as is digitalis to derange the digestion, although Penzoldt claims 
that gastric irritation may be evaded by giving the glucoside only 
when the stomach is full. The dose of digitoxin must at present 
be considered as unsettled, but one-quarter of a milligramme i-?^ 
grain) may be used with entire safety. 

Zeltner considers that one-quarter of a milligramme (^-J-^ grain) is equivalent 
to 0.235 gramme (3i grains) of powdered digitalis; or, in other words, that digi- 
toxin is about one thousand times stronger than the crude drug. Bosse considers 
one milligramme of digitoxin as equal to one gramme of digitalis (1 to 1000 
leaves), and has used the glucoside by enema up to two and one-half milligrammes 
a day with excellent results. Curioni gives the minimum ordinary single dose as 
one-half a milligramme ( T .V- grain), the maximum as one milligramme. 

Hypodermic Administration. — When it is desired to use digitalis 
hypodermically the tincture is the preparation commonly preferred, 
and in our experience it causes less irritation than do solutions of 
Merck's digitalin. It is claimed by D. E. Hughes that if the tincture 
be so prepared as to be free from fatty substances it is hypodermically 
non-irritant. The hypodermic use of the active principles of digitalis 
must at present be considered as tentative. 

Huchard affirms that by means of gentle warmth an oily solution of Nativelle's 
digitalin can be made which, when given hypodermically, acts efficiently, and 
does not cause local irritation, — dose, not to exceed one-sixty-fifth of a grain. It 
is stated by Madsen, of Copenhagen, that one cubic centimetre (16 minims) of so- 
called Pet it's solution will dissolve one milligramme (^ grain) of digitoxin. Of 
such a liquid four minims ( T ^. grain) is the hypodermic dose. Petit's solution: 
Glycerin, 333 parts; alcohol, 95 parts; water to 1000 parts. 

* Local irritation, and even the production of abscesses, have also been noted from "digitalin " 
by various observers besides ourselves. See Witkowski {Deutsches Archiv j. Klin. Med., xviii. 
142); also Pel {.Centralb. f. Med. Wiss., 1877, 169). 



236 GENERAL REMEDIES 

APOCYNUM. 

Apocynum cannabinum or dogbane (also incorrectly known as 
Canadian hemp) is a milky-juiced herb native to North America, 
growing to a height of from three to six feet and producing dense 
cymes of greenish-white flowers. The rhizome, which is the official 
portion, occurs in pieces varying in length, from one-eighth to one- 
third inch in diameter, of a greenish color and a bitter nauseous taste. 

Schmiedeberg has separated from apocynum two principles, to 
which he gave the name of apocynin and apocynein. The latter is 
a glucoside, while the precise nature of apocynin he did not determine. 
According to H. C. Wood, Jr., the substance furnished by Merck <fc 
Co. under the name of apocynin is inactive. 

Fluidextractum Apocyni 5 to 15 minims (0.3-1.0 C.c). 

Local Action. — Apocynum is so irritant to the alimentary tract 
that when given in full doses, it acts both as an emetic and cathartic, 
and has indeed been used clinically for these effects. 

Physiological Action. — There have been two studies of the 
physiological action of apocynum, one by Dotschewski and the other 
by H. C. Wood, Jr. In both these researches it was shown that the 
drug has an effect on the circulation similar to that of digitalis, caus- 
ing a marked rise of the blood-pressure with slowing of the pulse, 
followed, when the dose has been sufficiently large, by a marked 
increase in the rate of the pulse and a sudden cessation of the heart's 
action. Both of these investigators agree that the slowing of the pulse 
does not occur after division of the pneumogastric nerves, and it is 
therefore probably due to the stimulant effect upon the inhibitory 
centres. According to Dotschewski the elevation of the blood-pres- 
sure is largely dependent upon stimulation of the vaso-motor centres. 
In the experiments of H. C. Wood, Jr., however, section of the spinal 
cord did not lessen the power of apocynum to cause an elevation of 
the blood-pressure, and this observer attributes the elevation of the 
pressure either to stimulation of the cardiac muscle, or a stimulation 
of the arterial walls directly, or both. Since both investigators agree 
that there is a contraction of the vessels of the kidney, it seems prob- 
able that there is a stimulant influence directly upon the arterial 
walls. The character of the pulse-wave after the injection of this 
drug and the fact that the heart's action is arrested in systolic spasm, 
as after digitalis, renders it probable that the elevation of the blood- 
pressure is due to simultaneous stimulation of the heart and of the 
vascular system. ■ 

During the stage of rapid pulse electrical irritation of the vagus 
fails to slow the pulse, indicating that there is probably a late paraly- 
sis of the peripheral ends of the inhibitory nerves of the heart. 

Secretion of Urine. — According to Dotschewski a large dose of 
apocynum causes such a marked constriction of the kidney vessels 
in the normal animal as to greatly lessen the flow of urine and may 



CALM MAC STIMULANTS 237 

cause complete arrest of this secret ion. When, however, there has 
been a failure of renal activity brought about through the injection 
of a depressant drug as chloral, apocynum causes a re-establishmeni 

of the urinary secret ions. 

Nervous System. — The action of apocynum upon t ho nervous 
system is certainly a very feeble one, since Wood, Jr., found in the 
frog that after a dose sufficient to cause complete arrest of the heart 
there is still left some voluntary and reflex power, and that the 
motor nerve remains irritable for some time after death. 

Therapeutics. — The original observation of Knapp that apocy- 
num is a valuable diuretic in cases of dropsy, especially when de- 
pendent upon hepatic cirrhosis, has been confirmed by Griscom, 
Dabney, and many other observers. Lowry has also found the drug 
of value to aid in the elimination of fluid accumulating as the result 
of various cardiac lesions as well as in chronic Blight's disease. 

The irritant effect of the drug upon the mucous membranes very 
seriously interferes with its therapeutic use. According to Griscom, 
if given in sufficient dose it is both emetic and purgative. 

STROPHANTHUS. 

Under the names of Kombe, Inee, Onaye, and Pahouius poison, 
there have reached Europe various African arrow-poisons, which arc 
now believed to be derived from one or more species of the tropical 
genus Strophanthus, — apocynaceous climbing shrubs. The name of 
Strophanthus Kombe was given by Sir John Kirk to the tree which 
he first identified as the source of the Kombe poison; but botanists 
are at present agreed that the species is the Strophanthus hispidus of 
De Candolle. The seeds, which are the official part of the plant, are 
one-half to one inch in length, of a greenish-brown color, downy, and 
characterized by a long awn. They depend for their activity upon 
the presence of a glucoside strophanthin, of which they contain in 
the neighborhood of two per cent. This principle occurs as a white 
or faintly yellowish crystalline powder of an intensely bitter taste, 
freely soluble in water and in dilute alcohol, and sparingly soluble 
in absolute alcohol. 

Official Preparations : 

Tinctura Strophanthi (10 per cent.) 3 to 6 minims (0.2-0.3 C.c). 

Strophanthinum ^fo grain (0.3 Milligm.). 

Local Action. — Locally, strophanthus and strophanthin are 
exceedingly irritant to mucous membranes. Strophanthin is also an 
anesthetic, M. E. Gley having found that one-thousandth of a grain 
of strophanthin caused in the rabbit's eye not only a pronounced 
myosis but a very rapid and durable anesthesia. It is true that 
Steinbaugh concluded that this anesthetic action is not due to stro- 
phanthin but to some other constituent of strophanthus, but Hare 
and De Schweinitz have found that in this there was some mistake, 



238 GENERAL REMEDIES 

and that strophanthin itself is powerfully anesthetic, but is so irritant 
that its application to the eye may be followed by inflammation or 
even ulceration. 

Absorption and Elimination. — Strophanthus yields its active 
principle readily to absorption and elimination. It is therefore a 
promptly acting drug, but has sufficient permanency for the effects 
of a single dose to last some hours. 

Physiological Action.— In the healthy man strophanthus in 
sufficient dose produces fall in the rate of the pulse, with increase of 
force, without alteration of the respiration, but, if the dose has been 
large enough, with some gastric irritation and, according to Drasche, a 
slight fall of temperature. In Drasche's experiments the hypodermic 
injection of fifteen drops of the tincture induced violent local irrita- 
tion, repeated vomiting with nausea, pronounced diuresis, and a 
fall of the pulse. Twenty drops given by the mouth decreased the 
pulse thirty beats. 

In the lower animals strophanthus produces symptoms similar to those that it 
causes in man, the diarrhoea often being especially violent. No cases of human 
poisoning have been reported, but after fatal poisoning in the lower animals, evi- 
dences of irritation in the gastro-intestinal tract are usually present, and violent 
irritation and even inflammation of the secreting structure of the kidneys, with 
small hemorrhages, have been noted by several observers. Mairet and Combemale 
also state that the blood-globules are frequently altered, and the urine, before death, 
albuminous. The absence of nervous symptoms until very late in the poisoning 
shows how very little influence strophanthus has upon the nervous centres. An obser- 
vation upon the lower animals made by Mayeur and by Lemoine is of great practical 
interest, especially since similar results have been obtained by some of the German 
authorities in man. These observers found that strophanthus has a tendency to 
accumulate in the normal system, so that when small doses are given daily for a 
length of time, after a time violent and even fatal poisoning results. 

The first to make elaborate experiments with strophanthus was T. R. Fraser. 
One-twentieth of a grain of the extract of the seeds produced, in the frog, stiffness of 
the limbs and gradual loss of reflexes and of voluntary movements, the respiration 
continuing after the cessation of the heart's beat. 

Nervous System. — Upon the general nervous system strophanthus 
appears to have little or no action. It is true that Bahadhurji states 
that preceding the paralysis there is a stage of hyperesthesia, and 
that the motor nerve-trunks are affected by the drug, but these 
affirmations have not, that we are aware of, been confirmed. 

Muscles. — The chief physiological influence of strophanthus is as 
a muscle-poison. In Fraser's experiments, the muscles of a leg being 
protected from the poisoning by tying the arteries, galvanization of 
the nerve caused active contractions at a time when muscles else- 
where failed to respond to any irritation of their nerves or substance. 
The first influence of the poison upon the muscular fibre is to increase 
its tonicity, and when the muscle dies it does not go into relaxation, 
but passes directly from life into post-mortem rigidity. 

Respiration. — Both Langgaard and Fraser affirm that the fatal 
result in poisoning by strophanthus is due to cardiac arrest, but 
Mairet and Combemale, and also Bahadhurji state that at least in 



CARDIAC STIMULANTS 



239 



some instances there is a primary arrest of respiration, and, accord- 
ing to Mairet and Combemale, the respiration which is at first hurried 
is usually distinctly slowed before the fatal termination. There is, 
however, no sufficient proof that the drug acts upon the respiratory 
cent res, and though asphyxial death does occur, it is in all probability 
the result of the muscular influence of the poison. 

Circulation. — The effects of strophanthus upon the circulation are 
very similar to those produced by digitalis. There is the same slow- 
ing of the pulse with usually an increase in the blood-pressure, fol- 
lowed in the toxic dose with a rapid irregular heart and an extremely 
high pressure. In many cases, however, the blood-pressure does not 








Fig. 13. — Showing the Action of Strophanthin on the Frog's Heart. 
1. — Normal. 2. — Therapeutic stage. 3. — Toxic effects. 

fall at death with the same suddenness as in digitalis-poisoning, but 
there appears to be frequently a toxic relaxation of the heart-muscle. 
The therapeutic dose of strophanthus affects the heart precisely as 
does digitalis. There is, however, some reason for believing that the 
drug acts less powerfully upon the vaso-motor system than does digi- 
talis, although it is certain that the vessels are more or less constricted. 

Fraser proved that strophanthin has a direct action upon the heart of the 
frog, and in this has been confirmed by Bahadhurji, by Huchard, by Reusing, by 
Gley and Lapicque, and other observers. By minute doses the rate of the beat is 
lessened and the size and force of the aortic pulse-wave increased. 

It is noteworthy that Fraser and some other investigators have found that the 
frog's heart is arrested in systole, while Reusing and Huchard have seen it stop in 
diastole, and Paul Bert has noted in the cat both systolic and diastolic arrest. The 
muscle of the frog's heart, according to Fraser, is much more susceptible to the 
influence of strophanthin than the voluntary muscles, and passes rapidly into 
post-mortem rigidity, with acid reaction. 



240 GENERAL REMEDIES 

The combined testimony of Fraser, of Popper, of Gley, of Paschkis and Zerner, 
of Langgaard, and other investigators proves that moderate doses of strophanthus 
cause in mammals pronounced rise in the arterial pressure. As this occurs as well 
in curarized (Gley) as in normal animals, it must be due to a direct action of the 
drug, and not secondary to clianges in the respiration; after poisonous doses the 
pressure immediately or secondarily falls gradually to zero. The sphygmograplu'c 
work of Paschkis and Zerner shows that stroplianthus influences the blood-pressure 
in man as it does in the lower animals. 

The general muscular action of the drug would indicate that it has the power 
of stimulating muscle-fibres in the walls of the arterioles, and Bahadhurji asserts 
that the vessels can be seen to contract under its influence; while Popper found that 
section of the splanchnic nerve or of the cervical cord does not prevent the rise 
of the arterial pressure, — a fact which has been confirmed by Gottlieb and Magnus, 
who further demonstrated with the plethysmograph that there is marked contrac- 
tion in the size of the spleen evidently due to vascular constriction. In a second 
research the same observers found the size of the brain was increased rather than 
decreased by strophanthin, a change which is probably the outcome of the 
dominant influence of the splanchnic vessels upon the general blood-pressure. 

The slowing of the pulse is probably due to the direct action of the drug ujion 
the cardiac ganglia, Paschkis and Zerner * having found that in the dog it is not 
prevented by previous section of the vagus; Popper states that in the advanced 
poisoning there is peripheral paralysis of the vagus without alteration of the 
irritability of the accelerator nerves. 

Diuretic Action. — Although several observers have failed to notice 
an increase in the urinary secretion in man and in animals under the 
influence of strophanthus, yet the general testimony is too strong to 
be gainsaid; and it seems established that strophanthus acts not only 
in cases of cardiac disease but also in healthy men and animals as a 
powerful diuretic. This indicates that the drug has a direct stimulat- 
ing influence upon the secreting structure of the kidneys, a conclusion 
which is confirmed by the renal lesions of the poisoning, and also 
by the oncometric experiments of Phillips, which showed that 
strophanthus does not cause vascular congestion of the kidneys. 

SUMMARY. — Strophanthus is primarily a muscle-poison, whose 
influence, whatever it may be upon the nervous system, is so 
subordinate to its action upon the voluntary muscles and upon 
the circulation as to play little or no role in the poisoning. In 
concentrated form, however, it is paralyzant to the sensory 
nerves and probably to other portions of the nervous system. 
The most susceptible portion of the body to its influence is the 
cardiac muscle, upon "which and also probably upon the muscu- 
lar fibres of the walls of the vessels it acts as it does upon 
voluntary muscles. 

Therapeutics. — Strophanthus is used in practical medicine to 
meet exactly the same indications as those for which digitalis is 
prescribed. It is, however, less powerful and less certain in its in- 
fluence for good than is digitalis, but acts more promptly and more 
fugaciously. Its influence usually begins in half an hour and lasts 
from four to eight hours. It would seem to be indicated especially 

* These observers state that sometimes in the normal dog the slow pulse was wanting. 



CARDIAC STIMULANTS 241 

in cusps of acute heart-failure, but both its tincture and strophan- 
thin are locally too irritant for hypodermic use except in cases of 
groat emergency. When actively pushed, it probably is no better 
borne by the stomach than is digitalis; but experience has shown 
that some individuals are affected unpleasantly more quickly by 
strophanthus than they are by digitalis, while in others the opposite 
is the case. In chronic heart disease strophanthus stands next to 
digitalis in the list of useful heart tonics and stimulants, in some cases 
acting more favorably than digitalis for reasons not apparent, in 
others extremely useful in combination with digitalis, while in the 
majority of instances it is chiefly advantageous as a remedy to take 
the place of digitalis when it is from time to time suspended for the 
purposes of resting the stomach or preventing cumulative action. 
Its superiority as a diuretic makes it of especial value in cardiac 
dropsy. When given in overdose it produces burning in the oesoph- 
agus and the stomach, with gastric distress and severe vomiting. 

M. Furbringer reports three cases in which, after the remedy had been used in 
a large quantity and for a long time, sudden death from syncope occurred. It may 
well be that the death was directly caused by the strophanthus, but it is more prob- 
ably a parallel occurrence to what often happens in advanced cardiac disease treated 
with very large doses of digitalis. 

Zerner and Loaw have employed strophanthus with alleged 
success in Basedow's disease and in Bright' s disease, and they consider 
it especially useful in renal affections with secondary failure of the 
heart, a condition in which we have seen it act most advantageously. 
Rothziegel and Koralzewski and H. Haas commend it highly, not 
only in chronic but also in acute Bright's disease. 

Administration. — The U. S. Pharmacopoeia recognizes Stro- 
phanthin and officially describes it as "a glucoside or mixture of 
glucosides obtained from Strophanthus;" it also assigns to it the dose 
of one-two-hundredth of a grain (0.3 Mg.). Probably in many cases 
larger amounts than the official dose are necessary to obtain the 
desired therapeutic effect. Stahr affirms, as the result of clinical 
studies with Merck's crystalline strophanthin, that twenty milli- 
grammes, or three-tenths of a grain, may be given in twenty-four 
hours without producing serious results. 

SUPRARENAL GLANDS. 

The suprarenal glands* are two small bodies located above either 
kidney in all mammals. For medical purposes they are obtained from 
the sheep or from the ox. The gland freed from fat, dried and pow- 
dered, is recognized by the U. S. Pharmacopoeia. It occurs as a yel- 
lowish-brown, amorphous powder, with a faint somewhat meaty odor, 
yielding its activity to, although not completely dissolving in, water. 

* The suprarenal glands have in previous editions of this book been considered among the 
family of alteratives, but as they are used in medicine almost exclusively for their effects upon the 
circulation it has been thought much more in consonance with their physiological action and 
therapeutic uses to class them among the cardiac stimulants. 

16 



242 GENERAL REMEDIES 

Glandulae Suprarenales Sicca? 3 to 5 grains (0.2-0.3 Gm.). 

In 1897 Abel separated a body in the form of benzoyl-chloride 
from the suprarenal capsules, to which he gave the name of epineph- 
rin, and which possessed to a marked degree the characteristic 
physiological action of the adrenal glands. Subsequently he suc- 
ceeded in separating the pure base. In 1900 Von Furth separated 
an active body, to which he gave the name of suprarenin, and in 1901 
Takamine described a method by which he isolated a principle, to 
which he gave the name of adrenalin. 

All of these substances are extremely active stimulants to the circulation, as 
small a quantity as 0.016 milligramme (-foV<y g ram ) of adrenalin per kilo injected 
intravenously being sufficient to markedly elevate the blood-pressure. Abel regards 
adrenalin as an epinephrin hydrate, since he found that by dehydration, either 
with mineral acids or by heating in vacuum, adrenalin is converted into epinephrin. 
He insists on the formula for adrenalin of Ci H ]3 NO£H 2 O although most authorities 
agree on C 9 H 13 N0 3 . 

The stimulant principle of the suprarenal gland appears to be in 
the nature of a glandular secretion and has been found by both Dreyer 
and Ehrmann in the suprarenal vein. 

The observation of Pettit, that the adrenals are affected by 
glandular poisons, as pilocarpine, in the same manner as are the 
other glands of the body has been contradicted by Ehrmann. 

It is certain that the suprarenal glands have other functions besides elaboration 
of epinephrin, and they probably are concerned with the destruction of poisons, 
for Audenaysa, Boinet and Abelous have all shown that animals are more suscepti- 
ble to various poisons after the extirpation of these bodies. Langlois and Charrin 
discovered that the repeated injection of certain toxins in sublethal doses produced 
an hypertrophy of the suprarenal glands; but that instead of being physiologically 
more active, such hypertrophied glands lose their reaction towards ferric chloride 
and also their effects on the blood-pressure. The fact that the hypertrophied glands 
affect the circulation less than do the normal is very strong evidence that the circu- 
latory poison is not the same principle as the antitoxic substance.* 

It has long been known that the so-called Addison's disease, which is character- 
ized by a progressive asthenia, a peculiar bronzing of the skin, anemia, and loss of 
digestive power, with excessive vomiting, results from atrophic or destructive 
disease of the suprarenal glands, but the immediate cause of the symptoms has never 
been satisfactorily explained. 

Local Action. — Locally applied the extract of the suprarenals 
acts as a powerful constrictor of the blood-vessels. It has of itself 
no local anesthetic properties, but when used in conjunction with 
cocaine, enhances the powers of that drug, probably by preventing 
too rapid absorption (see Meltzer and Auer). 

Elimination. — The active principle of adrenals is very rapidly 
destroyed or eliminated in the system, since the effects do not last 
much over ten or fifteen minutes. Cybulski discovered that the 

* An interesting confirmation of the fact is the observation of Caussade that the glycerin 
extract of the suprarenals when injected continuously produces an hypertrophy of the suprarenals 
precisely as do other toxic bodies; suggesting that the gland destroys its own secretion when in 
excessive amount. 



CARDIAC STIMULANTS 243 

urine of animals poisoned with suprarenals is capable of producing a 

rise in the blood-pressure, and therefore believed that the active 
principle is eliminated by the kidneys. Ott and Harris confirm this 
fact, but assort that it can be shown only after enormous doses have 
been given. It would seem, therefore, that only a part of the drug 
is eliminated by the kidneys. Langlois found that maceration with 
the liver destroyed the active principle of the gland, that ligation of 
the hepatic vein prolonged the duration of its effect, and that when 
injected into the portal vein the suprarenal had comparatively small 
influence upon the circulation. This last fact has been also noted bj- 
Carnot and Joserand, who further determined that injection into 
the femoral artery likewise destroys the activity of adrenalin. It 
would seem, therefore, that it is largely oxidized in the liver and 
muscular tissue. Erhmann believes, however, that adrenalin is 
neither eliminated nor destroyed, because he finds remaining in the 
blood after the pressure has fallen to the normal more than sufficient of 
the principle to act as a circulatory stimulant, and because the blood of 
such an animal is capable of causing a rise of pressure in another animal. 

Physiological Action. — The most manifest action of suprarenal 
bodies is upon the circulation, so that after the exhibition of any- 
thing like the therapeutic dose the only symptoms produced are 
connected with the circulation. 

Toxic doses of the extract caused in the frog progressively increas- 
ing loss of power without a true paralysis, which seems to be of spinal 
origin, since Gourfein and Oliver and Schafer find that after ordi- 
nary toxic doses the nerve-trunks and muscles preserve their activity 
up to death; on the other hand, Vincent asserts that the suprarenal 
extract is a muscle-poison, producing, when given to the frog in over- 
whelming doses, a peculiar rigidity similar to that brought about 
by too much veratrine. 

According to Abel and Abbott, epinephrin kills by arrest of the 
respiration. This paralytic effect upon the respiratory centres is 
preceded, if the dose has not been too large, by an enormous increase 
in the rate of the breathing. The lethal dose for a rabbit, according 
to Abel, is about ten milligrammes. 

Nutrition. — Although the effect of suprarenal feeding on nutri- 
tion seems to be of minor importance, it has been abundantly proven 
that either the dried capsules or adrenalin is capable of producing 
glycosuria. This is accompanied with an increased amount of sugar 
in the blood and apparently disappearance of glycogen from the 
liver (see Paton). 

The injection of the suprarenal extract or its active principle has been shown 
by a number of observers to produce glycosuria. Croftan found in the suprarenal 
extract a diastatic ferment which was capable of producing glucose from glycogen, 
but Hurter and Richards have shown that Takamine's adrenalin does not affect 
solutions of glycogen, although it causes the occurrence of sugar in the urine. They 
attribute this effect to an action on the pancreas, since they found degeneration 
of the islands of Langerhans after adrenalin-poisoning. 



244 GENERAL REMEDIES 

Paton determined that adrenalin was capable of causing the formation of 
sugar from the proteids after the destruction of the carbohydrates of the body; 
the glycosuria he therefore regarded as a true diabetes. 

Drummond has shown that adrenalin is capable of giving rise to 
acute parenchymatous nephritis. 

Circulation. — As was first shown in 1895 by Oliver and Schafer 
and Szymonowicz and Cybulski, almost simultaneously, after the 
intravenous injection of the suprarenal extract or its active principle, 
there occurs an extraordinary rise of the blood-pressure accompanied 
by a slowing of the pulse. When the blood-pressure has reached its 
maximum, the pulse becomes rapid. This increase in the blood-pres- 
sure, which is of very short duration, is brought about by a simul- 
taneous stimulation of both arterial and cardiac muscles, or else 
their intrinsic ganglia. 

According to Cyon, the late increase in the rate of the pulse is brought about by 
a heightened excitability of the accelerator centre. Amberg has shown that the 
slowing of the pulse is not dependent upon a rise of the blood-pressure as is claimed 
by Gearheart, but is due to a stimulation of the inhibitory centre, being abolished 
either by section of the vagi or the injection of atropine. The rise of the pressure 
is not prevented by division of the splanchnics (Cyon) nor of the spinal cord (Oliver 
and Schafer). Meltzer and Meltzer and Josue have shown that the division of the 
sympathetic does not prevent the constriction of the vessels in the ear of the rabbit 
on the corresponding side. In fact, according to the former investigators, the 
contraction was more marked on the side whose nervous influences had been de- 
stroyed than on the other side. Gottlieb lias determined that the vessels of an 
isolated kidney which bad previously been dilated with hydrated chloral were 
contracted by the suprarenal extract. The pulmonary pressure, according to both 
Velich and Gearheart, is slightly elevated by the adrenals. 

Ott and Harris have found that adrenalin applied externally to the isolated 
frog's heart produces a temporary decrease of both force and rate followed by an 
increase in the same, and Gottlieb has found that the isolated mammalian heart is 
also stimulated by the suprarenal extract. With very large doses the rise of pres- 
sure is followed by a gradual fall to the zero point, the heart ceasing in diastole. 

In 1903, Josue announced the discovery of aortic arteriosclerosis 
following the injection of adrenalin. His observations have been 
repeatedly confirmed by Loeb and Githens and numerous other investi- 
gators. These lesions are usually the result of prolonged courses of 
injection, but Pierce and Bauldauf have observed distinct lesions 
of the aorta, and also of the heart, following the intravenous injec- 
tion of a single dose of one minim per kilogramme of 1: 1000 solution. 

The lesions produced have been limited to the aorta, usually to 
the arch. They differ markedly in their histological appearances 
from those seen in the human vascular degenerations, but as pointed 
out by Adler and Hensell, and also by Pierce and Stanton, these 
differences are not greater than might be expected when the difference 
in structure of the arterial walls is borne in mind. The question as 
to the cause of these lesions appears not yet to have been finally 
answered. The fact that both nicotine (see Adler and Hensell) and 
digitalis have been shown capable of producing similar lesions would 
argue that they were due chiefly to the increased blood-pressure. 



CARDIAC STIMULANTS 245 

On the other hand, Braun asserts that the consentaneous adminis- 
tration of amyl nit rite, which prevents rise of pressure, does not 
preclude the production of arteriosclerosis by the suprarenal. Pul- 
monary (edema has been reported by Kulbs and others as a secondary 
result of the use of adrenalin. 

Therapeutics. — There is at present considerable clinical as 
well as experimental evidence to show that the extract of the supra- 
renal capsule is of value in the treatment of Addison's disease. It is 
plain, however, that when the lesion of the adrenals is cancerous or 
tubercular, supplying artificially to the system an active principle 
prepared by those bodies cannot affect the progress of the local disease 
and therefore cannot bring about a cure. 

The most important therapeutic use of this drug depends upon 
its influence upon the blood-vessel walls when locally applied. It 
is used to counteract the vascular engorgement in the treatment 
of various inflammations of the mucous membranes, as rhinitis, 
pharyngitis, conjunctivitis and the like. 

According to Konigstein and De Schweinitz, the retinal vessels 
are not affected when the drug is instilled into the eye. It does not 
dilate the pupil* nor influence accommodation. It seems to possess 
the pow r er of penetrating the skin and of whitening the hyperemic 
skin of chronic eczema. 

It is difficult to say precisely what value this method of treatment 
has in acute inflammations. De Schweinitz is of the opinion that, 
although the application of the suprarenal solutions will produce a 
blanching of the inflamed part, it does not hasten the cure of the 
disease, and Kyle has seen cases of acute coryza made decidedly 
worse by the treatment. In hay fever it frequently gives good results, 
but in many cases fails entirely to relieve the symptoms. On account 
of its local vaso-constrictor action it is also of use in controlling local 
hemorrhages, as epistaxis, hematemesis, enteric hemorrhages in typhoid 
fever. Various authors recommend it for the purpose of preventing 
hemorrhage during operations on the throat and eye. As pointed 
out by Kyle, operations done under adrenalin ischemia are likely to 
be followed by post-operative bleeding. Its effect in constricting the 
blood-vessels is not likely to make it of any value as a styptic in 
internal hemorrhages. Carnot and Joserand have shown that if 
injected intravenously it does not produce visceral hemostasis. 
Moreover, these authors find that its action as a local styptic differs 
very markedly in different portions of the body. Thus, when injected 
in the kidneys, it has no hemostatic action at all; much less power 
when applied to the intestines or stomach, than in the nose. 

Suprarenal extract and its active principle have been suggested, 
and to a certain extent used, as circulatory stimulants in conditions 
of sudden circulatory failure, especially in shock during operation. 
The extreme fugaciousness of its action makes it, however, even in 

* Meltzer, Ott, and Harris assert that after section of the cervical sympathetic it does dilate 
the pupil. 



246 GENERAL REMEDIES 

these acute conditions, of comparatively little value, and the effects 
of its repeated use in causing arterial degeneration and pulmonary 
oedema, render its repeated use very dangerous. We have seen 
patients who, we believe, were being killed by confidence in this 
drug as a circulatory stimulant. Internally it has been recom- 
mended by Cohen for the relief of asthma and hay fever, and by 
Floersheim in endocarditis, but it is extremely doubtful if it is of 
value in either of these conditions. Schafer recommends its em- 
ployment in uterine hemorrhages, as does also Floersheim. The 
former believes that it controls the hemorrhage by stimulation of 
the uterine muscle. 

Administration. — Locally the suprarenal gland may be used 
in the form of a watery extract of from five to twenty per cent. Adren- 
alin may be applied in strengths varying from 1 to 1000 to 1 to 
10,000, either by atomizer or by tampon. Of the 1 to 1000 solution 
of adrenalin from five to thirty minims (0.3-2.0 C.c.) may be given 
hypodermically. In Addison's disease the crude gland is preferable 
to any of the active principles. 

CONVALLARIA. 

The rhizome with the roots of the lily of the valley, Convallaria 
majalis, is recognized by the U. S. Pharmacopoeia. It occurs in 
pieces of indefinite length about an eighth of an inch in diameter 
and somewhat branched. It has a characteristic odor and a bitterish 
somewhat acrid taste. 

In 1859 G. F. Walz discovered two active substances, convallarin 
and convallamarin. Of these, the first is crystalline, insoluble in 
water, and, according to W. Marme, when taken in doses of three or 
four grains, acts as a simple purgative. The glucoside convallamarin 
is soluble in water, and is the principle to which the plant owes its 
action upon the circulation. 

Fluidextractum Convallariae 5 to 15 minims (0.3-1.0 C.c). 

Physiological Action. — Marme found that convallamarin kills 
by a direct action upon the heart, and in moderate doses first slows 
and then quickens the pulse; previous division of the vagi did not 
interfere with the development of these phenomena. See finds that 
in the dog it first slows the action of the heart and increases the 
blood-pressure decidedly, the respirations at the same time becoming 
fuller and a little less frequent. If a toxic dose has been given, the 
heart's beats becomes very rapid and irregular, the arterial pressure 
still being much above normal; finally the pressure begins to fall, 
the cardiac pulsations to grow more feeble, and death occurs through 
syncope. It is stated that the pneumogastric nerves are weakened 
but never paralyzed, while the general nervous system is not affected. 
In man the action of the drug upon the circulation is as in the lower 
animals, and there is said to be usually produced profuse diuresis 



CARDIAC STIMULANTS 247 

and sometimes purging. In Isaew's experiments upon frogs with 
convallamarin, the heart was arrested in ventricular systole by two 
milligrammes of the pure convallamarin, the frog continuing to live 
for a long time, the remedy seemingly having no effect upon its general 
nervous or muscular system; isolating the heart had no effect upon 
the action of the poison. 

The fact that the heart is arrested in systole by convallamarin 
has been confirmed in the frog by Coze and Simon, in the dog by I. 
Ott, and it would appear, therefore, that the drug is a cardiac stimu- 
lant, more or less similar to digitalis in its action. Unfortunately, 
however, See affirms that in the dog the heart is arrested in diastole, 
that organ not being able to respond to the most powerful galvanic 
stimulant; Leubuscher states that convallamarin causes in the frog 
systolic cardiac arrest, but diastolic cardiac arrest in the mammal; 
and further, that in no doses does it in the mammal elevate the arterial 
pressure; while Leo Lowenthal, using the same preparation in exactly 
the same manner and dose upon different frogs of the same species, 
obtained diverse results which he himself was at a loss to explain. 
The evidence is so contradictory as to suggest that different observers 
have used different substances under one name. J. Nathanson asserts 
that the confusion is largely due to the impurity and lack of genuine- 
ness in the products used, even Merck himself having admitted that 
his commercial convallamarin is not the pure principle. Nathanson 
found that convallarin produced in man, when given in doses of 0.06 
to 0.12 gramme three or four times daily, only nausea, diarrhoea, 
and gastric pain; while convallamarin administered in daily amounts 
gradually increasing from 0.03 to 0.3 gramme reduced the rate of 
the pulse and markedly increased the flow of urine, only in very 
rare cases causing nausea or vomiting. 

Therapeutics. — The lily of the valley is said to have been 
long used by the Russian peasantry for the relief of dropsy, and in 
1880 Troitzky and Bojojawlewsky called attention to it as a valuable 
remedy in cardiac valvular disease, especially when associated with 
dropsy. See recommends it in palpitation of the heart, cardiac dilata- 
tion, fatty degeneration, and other forms of cardiac weakness, also in 
valvular lesions with failing heart-power; in a word, in the class of 
cases in which digitalis is now used. When there is dropsy, its posi- 
tive diuretic action renders it especially valuable, and in some cases 
it purges freely, probably through the convallarin. The value of the 
remedy has been confirmed by H. Desplats and by several other 
practitioners. Although condemned after trial by B. Stiller, by Pel, 
by Leyden, by Jacobi and Lubilinski, and by G. Leubuscher, it has 
been highly praised by Silvestrini and by E. Maragliana. E. Sansom 
gives as the result of his experience that convallamarin is very useful 
in mitral stenosis with failing of the heart. Marme found that the 
fatal dose of convallamarin was, for the dog, 0.015-0.03 gramme; 
for the cat, 0.005 gramme; for the rabbit, 0.006-0.008 gramme. 
S6e gives, of an aqueous extract of the whole plant, from fifteen to 



248 GENERAL REMEDIES 

twenty-three grains a day; Bojojawlewsky, each day an infusion 
representing from fifty to one hundred grains of the plant. The 
results obtained by Nathanson show that great caution must be 
exercised in the practical use of the active principles of convallaria. 

SPARTEINE. 

Sparteine is a liquid alkaloid obtained from the Cytisus Scoparius, 
or common broom plant. (See Scoparius.) It is colorless, of a 
penetrating odor and extremely bitter taste, soluble in alcohol, in 
ether, and in chloroform. Sparteine sulphate occurs in colorless 
prismatic crystals or granular powder, freely soluble in water and in 
alcohol, having a neutral reaction and a bitter, slightly saline taste.* 

Sparteine Sulphas i to J grain (0.015-0.03 Gm.). 

Physiological Action. — The ordinary therapeutic dose of 
sparteine produces no very definite symptoms, but Legris found 
that in doses of thirty centigrammes or over the alkaloid caused 
vertigo, headache, palpitations, and formications in the extremities; 
while Garand noted that forty centigrammes produced decided cardiac 
pain, with paraplegic paresis, these symptoms appearing about twenty 
minutes after the injection of the alkaloid, and reaching their 
maximum in from four to five hours. 

In the lower animals sparteine in large doses causes marked nervous disturb- 
ances. (See Husemann, Mitchell, Schroff, De Rymon, Griffe, and others.) There 
appear to be two stages of the poisoning. The first of these is characterized by 
trembling, incoordination of movements, increase of reflexes, clonic and tonic 
convulsions, embarrassment of respiration, acceleration of the pulse, and enfeeble- 
ment of the heart; the second, by enfeeblement of all the functions, the respiration 
becoming more and more depressed, and death preceded by convulsions occurring 
from respiratory paralysis. Fick found that by artificial respiration life may be 
prolonged for a very considerable period. 

Nervous System. — The conclusions reached by experimental physi- 
ologists in regard to the action of sparteine upon the nervous system 
are so contradictory as to imply that different alkaloids have been 
used under one name, one group of observers finding a palsy of 
central origin and the other concluding that the drug paralyzes the 
peripheral nerves. 

According to Fick and Mitchell, sparteine has a distinct influence upon the 
cerebrum; and Fick, Gluzinski, and other observers have found that the loss of 
reflex activity and the fatal arrest of respiration are due to centric paralysis; while 
De Rymon, Griffe, and Gluzinski are in accord in affirming that neither the motor 
nor sensory nerves are affected. In this they are confirmed by Cerna, who even 
states that the local application of strong solutions has no sensible effect upon the 
nerves. On the other hand, Fick and Mitchell state that the motor nerves are 

* The hydrochlorate of ozysparteine, an oxidation product from sparteine, is freely soluble 
in water, and has been used with asserted good results hypodermically by Von Oefele, in dose of 
six-tenths of a grain, as an active cardiac stimulant. See K. Hiirthle (Arch. f. Exper. Path. u. 
Pharrn., 1892). 



CARDIAC STIMULANTS 249 

attacked, and A. R, Cushny and S. A. Matthews find thai sparteine is closely related 
in its physiological action to conivun, its chief influence being upon bhe peripheral 
motor nerve-endings in the muscle, whereby it causes a paralytic asphyxia. Guinard 
and Gclcy slate that sparteine locally applied paralyzes the sensory nerves in the 
eye, and may even be substituted for cocaine in operations upon the eye. 

Muto and Ishizaka conclude (hat the fatal failure of respiration 
of sparteine-poisoning is due to the depressing action of the drug 
upon the peripheral phrenic nerve as well as to an action upon the 
respiratory centres. 

Circulation. — Although the subject of the action of sparteine 
upon the circulation has been investigated by Laborde, Griffe, Ga- 
rand, Masius, Gluzinski, Cerna, A. R. Cushny and S. A. Matthews, 
the results reached have been so discordant as to make their recon- 
ciliation at present impossible. The chief facts, that seem to us to 
be fixed, are that a sufficient dose of the alkaloid produces a pro- 
nounced fall of the arterial pressure, which is, at least in part, due to 
a direct action of the drug upon the heart. The more important 
question, whether the small dose of sparteine is or is not a cardiac 
stimulant, cannot at this time be finally answered. 

The effect of the alkaloid upon the pulse-rate in its fullest serial development 
appears to be a primary slowing, followed by an acceleration, which in turn gives 
way to a pronounced decrease below the normal. The size of the dose is a very 
potent factor in determining the action on the pulse-rate; thus, if a very large dose 
is given the pulse at once becomes slow and remains slow. Again, the slowing 
before acceleration of the pulse lias not been noted by various observers, and prob- 
ably occurs only after very small doses, and in some cases, according to the researches 
of Gluzinski, it is due to a primary excitement of the vagi nerve. Fick, Griffe, 
Garand, Masius, Gluzinski, and Cushny and Matthews are in accord in stating that 
the acceleration of the pulse is due to peripheral paralysis of the pneumogastric 
nerves, with its consequent withdrawal of inhibition, while it seems to be proved 
that the final slowing of the pulse is the outcome of a direct impulse of the spar- 
teine upon the heart itself. Neither muscarine (Fick) nor atropine (Cushny and 
Matthews) prevents the action of sparteine upon the heart. 

Garand, Gluzinski, Pawlow, and Cerna all affirm as the result of their own 
experiments that there is a distinct primary stage of increased arterial pressure; 
and in the experiments of Cushny and Matthews such rise of pressure immediately 
followed the injection of five milligrammes of the alkaloid into the veins of rabbits 
and cats, whether they had or had not been paralyzed with curare or other drugs. 
According to Pawlow, this rise of blood-pressure is due chiefly to stimulation of the 
vaso-motor centres; while Cerna reached the conclusion that it is caused partly by 
an increased activity of the heart and partly by centric vaso-motor stimulation. 
Cerna compares the action of sparteine to that of digitalis. Cushny and Matthews 
conclude that sparteine is entirely apart from digitalis in that it does not prolong 
systole, but slows the pulse simply by increasing diastole; and in that it favors 
excessive dilatation of the heart, and in any dose is a sedative rather than a stimu- 
lant to the viscus. They find that in the mammal the rise of blood-pressure is very 
brief and does not occur when the drug is given by the stomach. They conclude 
that the rise is not due to any specific influence of the sparteine, but is called forth 
by local irritation. 

Muscles. — When applied locally to the muscles, sparteine has 
some influence in diminishing their excitability and prolonging the 
duration of the latent period (De Rymon, Griffe. and Gluzinski). 



250 GENERAL REMEDIES 

But it does not destroy the functional activity of the muscles, even 
when brought in direct contact with them in a concentrated form, 
and its muscular influence is too feeble to be manifested in general 
poisoning. 

Kidneys. — It is still doubtful whether sparteine does or does not 
fully represent the diuretic influence of scoparius. Griffe affirms that 
in his experiments upon rabbits it produced absolute decrease in 
the excretion of urine, and although some clinicians assert that it 
acts in a man as a distinct diuretic, others affirm that any increased 
diuresis is secondary to the regulation of the circulation. 

Therapeutics. — The use of sparteine in diseases of the heart 
has been studied by a number of clinicians, notably See, Garand, 
Roland, Voit, J. M. Clarke, Kurloff, and Pawinski, who are all in 
accord in affirming it to be of value in the treatment of cardiac affec- 
tions, in which it slows the pulse and renders it more regular, increases 
diuresis, and is superior to most other cardiac remedies in its power 
of controlling general nervous excitement. Pawinski states that in 
pure nervous palpitation it exceeds digitalis in power and certainty 
in action, and that it is a valuable sedative in hysteria, neurasthenia, 
and allied conditions. Both Pawinski and See assert that it has a 
remarkable power of regulating the heart's action; the latter observer, 
indeed, affirms that no known remedy equals it for the purpose of 
making an irregular pulse regular. On the other hand, Pawinski 
warns against its use in cases in which the heart-muscle is believed 
to have undergone degeneration. Its action is a rapid one, the symp- 
toms produced by it, according to Clarke, See, and others, developing 
in thirty minutes to an hour after its ingestion, and continuing for 
five or six hours. According to Clarke, these symptoms consist 
primarily of a marked retardation of the pulse, with increase of the 
force and of the arterial tension, the skin at the same time becoming 
red and moist, while the respiration, which is at first quickened, 
soon becomes slower and fuller than normal. In overdoses it is said 
to cause very high tension of the pulse, with sharp cutting or throb- 
bing pains in the cardiac region, and sometimes nausea. It has been 
employed with asserted excellent results in all forms of valvular 
disease, in asthma, and especially in functional cardiac derangements. 
The very important statement made by Clarke, that it will control 
the pulse-rate and general symptoms in Graves's disease, receives 
some confirmation in the work of Pawinski and in our own experience. 
Some clinicians, notably Hans Leo, and Hiero Stoessel, have found 
sparteine, however, a very uncertain remedy. We do not believe 
that for general purposes it nearly equals digitalis; in our own trials 
with it in organic cardiac cases the results have been very unsatis- 
factory. It may be useful as a succedaneum to digitalis, and even 
as a substitute in neurotic cases. Pawinski gives 0.016 to 0.04 gramme 
three times a day, increasing gradually to 0.6 gramme during the 
twenty-four hours. The statements of Guinard and Geley, that 
sparteine may be used successfully externally like guaiacol for an 



CARDIAC STIMULANTS 251 

antipyretic, are strongly contradicted by Lannois. The sulphate 
may be used in pill or solution in commencing dose from one-quarter 
to one-half a grain (0.016-0.03 6m.), cautiously increased to two 
grains (0.13 Gm.) if required, and repeated every six to eight hours. 

ADONIDIN. 

Adonis veraalis, a plant of Northern Europe and Asia, contains 
a glucoside to which Cervello has given the name of adonidin. Accord- 
ing to Cervello, adonidin causes in the frog first increase in the force 
of the systolic contractions, then irregularity of rhythm with long 
diastolic pauses, and finally arrest in violent systole, the most char- 
acteristic phenomenon being the peristaltic movements which pre- 
cede the cardiac arrest. According to H. A. Hare, adonidin first 
increases and then slows the rate of the beat in the cut-out frog's 
heart, while its injection into the frog is followed by a period of slow- 
ing of the cardiac movements, with long diastolic pauses, succeeded 
by great increase of the pulse-rate, which in turn gives way to slow 
movement, ending in arrest. The heart, either within or without 
the body, stops in diastole. Although Cervello and also Guirlet 
state that the heart is arrested in systole, Hare affirms that, whether 
the heart be isolated or in situ, the arrest is diastolic. The contra- 
diction is not easily explained, unless it be through the observation 
of Guirlet. that in the rabbit he has seen the left ventricle in perma- 
nent systolic contraction, with the other cavities dilated and full of 
blood. The slowing of the pulse noted by Hare was found by him to 
be due to stimulation of the pneumogastrics, as it was prevented by 
their section. That the diastolic arrest was not merely an occasional 
phenomenon the result of excessive inhibition, as is sometimes seen 
from digitalis, was proved by its occurring after section of the vagi, 
as well as by the fact that galvanization of these nerves in the later 
stages of the poisoning failed to inhibit the heart, the nerves appear- 
ing to be paralyzed. According to Kakowski adonidin differs from 
the other heart tonics in that it produces a dilatation instead of a 
contraction of the coronary arteries. 

In Hare's experiments adonidin increased very distinctly the 
arterial pressure in the dog, while decreasing the pulse-rate. After 
large doses the first rise is followed by a marked fall of arterial pres- 
sure, with irregularity of the heart's action, and finally diastolic 
arrest. The experiments of Cervello and of Bubnow are in accord 
with those of Hare in showing that the drug produces first rise and 
then fall of pressure. Hare found that in animals whose spinal cord 
had been previously cut, a rise of pressure followed the exhibition of 
adonidin, but was not so great as in the normal dog, so that it is 
possible that the drug acts as a stimulant not only on the heart but 
also on the vaso-motor system. The first slowing of the pulse, ac- 
cording to Hare, is the result of stimulation of the inhibitory nerves, 
since it was prevented by their previous section, while the final fall 



252 



GENERAL REMEDIES 



of pressure is, at least in part, due to the vaso-motor palsy, since 
neither galvanization of the sciatic nerve nor asphyxia had any effect 
at a time when the heart had still considerable power. 

Therapeutics. — In 1879 Adonis vernalis was introduced to 
the medical world as a cardiac stimulant by Bubnow, a pupil of 
Botkin. Since then it has been tested by a number of physicians, 
with fairly concordant results. The general testimony is that its 
action in disease resembles that of digitalis, and that it is useful in 
the same class of cases. It is much more prompt than is digitalis, 
and Durand affirms that it has no cumulative tendency. There has 
been some difference of opinion in regard to its diuretic action, and 
whatever of such influence it has must be attributed to its action 
upon the circulation in the kidneys rather than to any marked direct 
power over the secreting structure. Durand asserts that it never 
produces disturbances of the alimentary canal, but Lublinski and 
Huchard have both seen it produce so much vomiting or diarrhoea 
as to require its withdrawal. In a case reported by Durand in which 
by mistake three grains of adonidin were given every half-hour, 
violent vomiting and diarrhoea were the most troublesome symptoms. 
Bubnow employed the infusion made from the whole herb four to 
eight parts in one hundred and eighty parts of water, and of this he 
administered a tablespoonful every two hours. Durand gives the 
dose of adonidin as 0.02 centigramme (one-third of a grain) every 
three or four hours. 



REFERENCES. 



AMMONIUM. 



ALCOHOL. 



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Dehio Centralb. f. Nerv. u. Psych., 

1895. 



CARDIAC STIMULANTS 



253 



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Zugsmitii Amer. Med., 1901. 



254 



GENERAL REMEDIES 



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APOCYNUM. 

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Dotschewski ... .Wiener Klin. Rundschau, 
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STROPHANTHUS. 

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CARDIAC STIMULANTS 



255 



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JOHANNSEN. . 
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I.KVKN 

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RmCHBBT T. Q„ April, 1890. 

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Wing An. O., 1903, xii. 



FAMILY II.— CARDIAC DEPRESSANTS. 



There are certain drugs which are used by practitioners to decrease 
the activity of the circulation, and it is these which are here considered 
under the heading of Cardiac Depressants. Many, in fact all of them, 
possess other powers besides those which cause them to be considered 
under this caption, and none of them are in very close accord in these 
qualities. There is, however, a general resemblance in the action of 
such as are derived from the vegetable kingdom, in that they are all 
depressants to the motor nervous system and yet all produce con- 
vulsions. H. C. Wood has made an especial experimental study of 
these convulsions, and has found that they are cerebral and not spinal, 
because they do not occur in any part of the body separated by section 
of the cord from cerebral influence. Further, they are probably due 
to disturbance of the circulation at the base of the brain, for the 
following reasons, the truth of each of which has been experimentally 
determined: first, lessening of the circulation at the base of the brain 
will cause convulsions; secondly, the convulsions produced by the 
cardiac depressants do not occur until the arterial pressure is reduced 
about one-half; thirdly, if the disturbance of the cerebral circulation 
be artificially increased by tying the carotids previous to poisoning, 
or in any other way, the convulsions come on sooner and are more 
violent; fourthly, in some animals the convulsions caused by arresting 
circulation at the base of the brain are feeble and ill-defined, while in 
others they are violent, and in species of the first order cardiac depres- 
sants produce but slight convulsions, while in species of the second 
order they cause violent convulsions. 

The indications for the use of a cardiac depressant may be said to 
be increased arterial tension, sthenic fevers, and severe local 
inflammations. In order that a rational selection of the various drugs 
may be made for any individual case, it is necessary to study how, in 
these various conditions, relief is afforded by an arterial sedative. 
When there is circulatory excitement from irritation or excitement of 
the heart, the mode of relief is too obvious to need discussion. It is 
plain that in such a case a drug should be selected which simply de- 
presses the heart's action and does nothing more. When there is 
severe inflammation, such as pneumonia, with high arterial tension, 
the effect desired is a lessening of the flow of blood to the part. A 
simple cardiac depressant may do this by lowering the force of the 
circulation, but a vaso-motor depressant is far more powerful. 
The blood-vessels of the inflamed part are already dilated, and conse- 
quently attract blood, as it were, to the part. If the remedy dilates 
256 



CARDIAC DEPRESSANTS 257 

all the blood-vessels, this local attraction ceases, and blood is diverted 
from the inflamed tissue. It would appear from the experiments of 
Ludwig, Schiff, and others that the blood-vessels of the body, after 
complete dilatation, are able to hold twice their normal amount of 
blood, and Golz (quoted by Fothergill) found that the intestinal vessels 
by themselves were able to contain all the blood of the body. These 
facts show how by means of an arterial sedative, which paralyzes the 
vaso-motor centres, ''we can bleed a man into his own blood-vessels," 
or, in other words, get much of the effect of a venesection by drawing 
blood from the diseased part. 

ANTIMONY. 

The only salt of antimony which is used to any extent in practical 
medicine is the antimony and potassium tartrate, or tartar emetic. 
This occurs in the form of transparent, efflorescent crystals, or as a 
white, granular powder. 

Its taste is at first very slight, but after a time styptic and acrid. 
In some persons it blisters the tongue and lips after a few moments 
of contact. Tartar emetic is insoluble in absolute but soluble in 
dilute alcohol, soluble in from two to three parts of boiling water, 
and in fifteen and a half parts of water at 77° F. It is incompatible 
with alkalies and with acids, including tannic acid and substances 
containing it. 

Official Preparations : 

Antimonii et Potassii Tartratis 

[Tartar Emetic] { £ ^in (expectorant) , (000 ^ 03 Gm } 

L J ( J grain (emetic) | 

Vinum Antimonii (0.4 per cent.)- . . .15 minims to 1 fluidrachm (1-4 C.c). 

Syrupus Scillse Compositus (0.2 per 

cent.) I to 1 fluidrachm (2-i C.c). 

Local Action. — Locally applied, tartar emetic is an irritant, acting 
upon some very delicate and susceptible skins in a very short time. 
In most instances, however, its continuous application for several 
days is necessary to produce any effect. At first there is simply a 
redness, accompanied by some burning pain and the eruption of small 
papules, which shortly become converted into vesicles and then into 
pustules. These are irregular in shape and size, varying from one- 
eighth of an inch to an inch and a half in diameter, and are very pain- 
ful. Sometimes these pustules give rise to small sloughs, but generally, 
if the application be withdrawn, they simply give origin to superficial 
ulcers, which readily heal. 

Absorption and Elimination. — Tartar emetic is very rapidly ab- 
sorbed in the gastro-intestinal tract, and elimination commences 
almost at once. The minute dose probably escapes from the system 
altogether through the kidneys, but the toxic dose is certainly thrown 
off with the secretions from the whole length of the gastro-intestinal 
17 



258 GENERAL REMEDIES 

tract, and probably also escapes with the saliva. Elimination is, 
however, not complete, so that in cases of fatal poisoning antimony 
may be found in the various tissues of the body. 

Masoin believes that the fixation of the antimony in the tissue begins almost at 
once, because he found that if he gave to the rabbit the minimum fatal dose of 
tartar emetic, then bled and practised transfusion either with blood from another 
rabbit or with normal salt solution, the animal died as quickly as did the animal 
left to the action of the poison; although when five or six times the minimum fatal 
dose was given bleeding and transfusion greatly protracted life. Moreover, blood 
drawn from the animal poisoned with the minimum fatal dose was only slightly toxic. 

Circulation. — In man and in all mammals any dose of tartar 
emetic, which is sufficient to affect the circulation, produces a steady 
fall of the arterial pressure, with a pulse-rate which may be at first 
slowed but soon becomes more rapid than the normal. The fall of 
pressure is due chiefly to a debilitating influence on the heart, although 
there is evidence that the vaso-motor mechanism is also depressed. 

In the lower animals all doses of antimony sufficient to cause any apparent 
effect progressively lower the arterial pressure; the pulse is sometimes at first tem- 
porarily accelerated, but usually the slowing of the pulse occurs from the beginning 
of the poisoning. During this period of slow pulse the diastolic pauses are extremely 
long and the pulse-waves greatly augmented, it may be to five times their original 
size. After a time the pulse usually becomes very rapid, the pulse-waves very small, 
the arterial pressure almost extinguished, and in a few minutes diastolic arrest 
occurs (Ackermann, Ernst Sentz). In the poisoned frog the cardiac contractions 
are from the beginning lessened in frequency and force, then become more rapid 
but extremely irregular, with the auricles pulsating more frequently than the ven- 
tricles (Radziejewski, Ackermann, Nobiling). The peripheral vagi are paralyzed 
so that the diastolic arrest is not inhibitory (Radziejewski). Antimony paralyzes 
the isolated frog's heart., destroying the irritability of the muscle (Ackermann); 
digitalis is stated to produce immediate restoration of function (I. Soloweitschyk). 

Antimony is certainly a direct cardiac depressant and paralyzant, but the 
assertion of Soloweitschyk that galvanization of the vaso-motor centre does not 
elevate the arterial pressure while the heart, is still active, taken together with the 
fact that the arterial pressure falls while the heart is apparently putting forth 
its normal force, indicates that the poison also depresses either centrically or 
peripherally the blood-vessel system. 

Nervous System. — The occurrence in man of anesthesia during 
antimonial-poisoning has been overlooked, but has been a marked 
feature in experimental poisonings. According to Radziejewski, the 
thermic sense is first paralyzed and later the tactile power. Radzie- 
jewski and Soloweitschyk have found that the depression of reflex 
activity occurs after, as before, section of the cord, and is therefore 
not due to stimulation of the Setschenow inhibitory centre; also 
that it is not prevented by tying an artery and cutting off access of 
the poison to the nerve, and is therefore not peripheral. It conse- 
quently must be spinal; and, as both observers noted that in the 
frog and the rabbit voluntary movements persist after the total 
abolition of sensibility and reflex activity, antimony must be a 
paralyzant of the receptive centres or sensory tract of the spinal cord. 



CARDIAC DEPRESSANTS 2. r ><) 

The motor cord probably shares to a slight extent in the depressing 
influence. The motor nerves and muscles are said to retain their 
functional power. 

Temperature. — The influence of antimony upon the temperature 
appears not to be very marked when the drug is exhibited in ordinary 
therapeutic doses. Ackermann affirms that, after doses severe enough 
to induce violent vomiting, the centric temperature is not lowered, 
although that of the extremities may fall as much as 3.5° C. After 
poisonous doses of antimony the decrease is very perceptible.* 

Abdominal Organs. — Tartar emetic acts as an irritant upon the 
whole alimentary mucous membrane. The serous discharges from 
the stomach and from the bowels may be to a certain degree due to 
the local irritant influence of the poison, but probably to a much 
larger degree are the outcome of an attempt to eliminate the drug 
circulating in the blood. 

Brinton proved that when tartar emetic was injected into the vein of an animal 
it was very freely and rapidly eliminated by the stomach. B. W. Richardson has 
corroborated this, and has also found t hut a similar elimination follows the inhala- 
tion of antimoniated hydrogen. Radziejewski's theory that the emesis is due solely 
to a local action of the poison is completely disproved by the experiments of Ma- 
gendie (confirmed by Brinton), in which vomiting was produced by tartar emetic 
after the stomach had been removed and a pig's bladder substituted. The vomiting 
caused by tartar emetic must therefore be, at least in part, of centric origin, but 
Mosso has proved that the local action of the drug also plays an important role in 
the production of vomiting; finding that when the tartar emetic is given by the 
mouth, vomiting is caused by smaller quantities and more promptly than when the 
poison is injected into the veins. 

Respiratory Organs. — The respiration in poisoning by antimony is 
very irregular, with all sorts of variations in the rhythm of the act, 
and is probably centrally depressed. 

In the advanced stages the pauses are often very long, and the inspiration and 
expiration so forced and prolonged that very generally, in animals at least, mar- 
ginal emphysema and subpleural ecchymoses are found after death. The origin 
of the respiratory trouble is probably somewhat complex, the chief factor being 
the direct influence of the drug upon the respiratory nerve-centres, and minor causes 
the intense venous congestion due to the failure of the circulation and the alteration 
of the blood itself. 

Upon the mucous membrane of the lungs antimony acts directly 
or indirectly, even in moderate doses, as is shown by clinical experience 
and by the experiments of Mayerhofer. 

Therapeutics. — There are three indications to meet which antimony 
and potassium tartrate is constantly employed. The first of these it 
fulfils by virtue of its powers as an emetic. The discussion of this 
may be found in the chapter upon Emetics. 

The second purpose for which antimony is used is to depress arterial 
excitement. It is chiefly in inflammation that tartar emetic is used 

* Ackermann found that a fall of only 1.0° C. occurred in rabbits killed in an hour, but in 
those that lived five hours the depression amounted to 6.6° C. 



260 GENERAL REMEDIES 

as an arterial sedative. In combination with more decided diaphoretics 
it is constantly employed by some surgeons in gonorrhoea and in various 
sthenic inflammatory affections. In 'pneumonia it has been very 
largely used, forming an essential portion of the old so-called contra- 
stimulant plan of treating that disease. According to the method 
of Rasori, four or five grains a day were at first given, but rapidly 
increased to twenty-four or even thirty grains daily. Although by the 
aid of opiates and careful dilution a species of tolerance was often 
obtained for these heroic doses, the method has very properly been 
abandoned by modern therapeutists. Whenever tartar emetic is 
given in such quantities as markedly to depress the circulation, by 
the vomiting and purging which it causes, it produces in the patient 
exhaustion as well as depression. Further, by the continuance of its 
local influence upon the intestinal tract after the period of depression, 
it interferes with the digestion of food and consequently with the 
regaining of power. On the contrary, neither aconite nor veratrum 
directly exhausts, though they powerfully depress. They are, there- 
fore, always preferable to tartar emetic when in a pneumonia or other 
disease it is desired to produce a temporary pronounced depression of 
the circulation. In fact, tartar emetic should never be employed 
as an active depressant of the circulation. 

Owing to its action upon the mucous membrane of the bronchial 
tubes, in the first stages of bronchitis tartar emetic is a valuable remedy. 
After free secretion has been established, other expectorants are, we 
think, of more service. It should be used only in sthenic cases, and 
never, unless in the most minute dose, in children or the aged. 

As a counter-irritant, tartar emetic is used only when it is desired 
to produce a slow, persistent, and at the same time very decided 
impression. For further discussion of its application to disease, see 
the chapter on Rubefacients. 

Toxicology. — The symptoms of antimony-poisoning are — nausea, 
violent vomiting and retching, with marked reduction of the force 
of the pulse, great muscular relaxation, and a feeling of faintness. 
At the same time the saliva is generally increased in amount 
and the skin is bedewed with sweat. The vomiting is violent, repeated, 
continuously re-excited by the slightest provocation, and is accom- 
panied by burning in the oesophagus and stomach and by colickj' 
pains in the abdomen. The matters vomited are first mucus, then 
mucus with bile, and finally, in some cases, blood. With the gastric 
disturbance occurs violent and frequent serous purging, the discharges 
resembling those of cholera, but becoming in some cases towards the 
last bloody. Cramps may occur in the extremities, and, in conjunction 
with the serous purging, have caused the antimonial-poisoning to be 
mistaken for cholera. The exhaustion is extreme, and deepens into 
collapse, with thready or imperceptible pulse, pinched, livid counten- 
ance, suppressed voice, profuse cold sweats, lowered temperature, 
and at last death from asthenia, generally preceded by stupor or con- 
vulsions: indeed, Taylor reports cases in which wild delirium was 



CARDIAC DEPRESSANTS 261 

present some hours before death. The urine* in mild cases is increased 
in quantity, as it is also in the beginning even in fatal cases, but in 
such towards the close it is generally scanty and bloody, and even 
suppressed. 

There has been described a Form of antimonial-poisoning in which neither 
vomiting nor purging! occurs, the symptoms being simply intense prostration, 
cold clammy sweat, a sense of oppression in the chest, with the respiration at first 
increased, then diminished in frequency and embarrassed; a rapid feeble pulse, 
altera time becoming slow, intermittent, and irregular; delirium, unconsciousness, 
tremblings, and clonic and tonic convulsions (Ilusemann). Tardieu states that in 
some cases of tartar emetic poisoning a rash, exactly resembling that produced by 
the external application of the drug, has appeared all over the body on the fourth 
or fifth day. 

The symptoms of antimonial-poisoning so closely resemble those 
of arsenical-poisoning and of choleraic diarrhoea, that when there is 
no distinct history, certainty of diagnosis can only be reached by an 
analysis of the excretions. In any suspected case of poisoning it is 
the duty of the practitioner to save the urine for chemical examination. 

The lesions of gastro-enteritis which are usually found after death 
from tartar emetic are sometimes not present. { The venous system is 
generally very much engorged, and the viscera are intensely congested. 
Magendie asserted that in animals poisoned by tartar emetic the 
lungs are always full of portions apparently hepatized; but Acker- 
mann, in twenty experiments, found only some marginal emphy- 
sema and subpleural ecchymoses, with, in one or two cases, spots of 
atelectasis in the lungs. The assertion of Magendie, therefore, is 
too sweeping; but it is true that, in a large proportion of fatal cases 
of antimonial-poisoning, emphysema, pulmonary apoplexy, atelectasis, 
or other structural lesions of the lungs exist. The blood usually 
coagulates imperfectly. 

Solkowsky, of Moscow, has found that when animals are fed upon 
antimonic acid (one-half to one gramme daily) or other preparations 
of the metal for from fourteen to nineteen days, the liver, kidneys, 
and even the heart undergo fatty degeneration; also that there is a 
lessening of the amount of glycogen in the liver, and in some cases 
even a total disappearance of it. This has been confirmed by Grohe 
and Mosler, who state that in the duchy of Brunswick the peasantry 
give to the geese, when producing the famous fatty livers, a certain 
quantity of the white antimony oxide every day. 

The minimum fatal dose of tartar emetic is not known. Three- 
quarters of a grain in a child, and two grains in an adult, have proved 
fatal, but in the latter case extrinsic circumstances favored the 

* What is said in the text is, we think, correct, although authorities differ on this point. Trous- 
seau (Traite de Therapeutique, 4th ed., i. 019) affirms that it is suppressed; Husemann, that it 
is never suppressed (Toxicologie, 854); Tardieu, that it is scanty. For a case in which it was sup- 
pressed, see Taylor's Medical Jurisprudence, London, 1873, 309. C. Gathgens (Centralbl. f. Med. 
Witt., 1870, 321) found, in some incomplete experiments, an increase of the elimination of urea 
after repeated non-toxic doses of antimony. 

tHusemann states this. Although vomiting is absent in these cases, purging is generally 
present. We do not remember to have seen the report of a case in which it was absent. 

{For cases, see Archives Gin., September, 1865. 



262 GENERAL REMEDIES 

result (Taylor, an analysis of thirty-seven fatal cases); two hundred 
grains have been recovered from; also one hundred and seventy 
grains.* 

The treatment of antimonial-poisoning consists in washing out the 
alimentary canal with large draughts of tannic acid, — the best known 
antidote, — in the free administration of opium by the mouth or 
rectum, or hypodermically if it cannot be retained, the hypodermic 
injections of strychnine and digitalis if the circulation fails, and 
the maintenance of the bodily temperature by external application 
of heat. 

Chronic Poisoning. — The symptoms following the criminal repeated 
administration of small toxic doses of tartar emetic, at intervals, 
are — nausea, mucous and bilious vomiting, watery purging, often 
followed by constipation, small frequent pulse, and asthenia, 
deepening into death from exhaustion. 

VERATRUM.f 

The U. S. Pharmacopoeia formerly recognized under the name of 
Veratrum viride the rhizomes and roots of that North American 
plant. Very unfortunately, at the recent Eighth Revision of the 
Pharmacopoeia, Veratrum viride was dropped as an official title and 
Veratrum defined as the dried rhizome and roots of Veratrum viride 
and Veratrum album. 

These two plants, one a native of North America, the other of Europe, are so 
closely allied that by many botanists they have been thought to be identical, though 
at present they are by most authorities believed to be distinct. The rhizomes are 
very similar in appearance and probably contain the same alkaloids and resemble 
one another very closely in their physiological action (see H. C. Wood and H. C. 
Wood, Jr.). But similarity is not identity, and both the chemical and toxicological 
evidence indicates that the European plant is stronger than is the North American, 
and that the two rhizomes probably differ essentially in the proportionate amounts 
of the various alkaloids contained in them. A number of cases of fatal poisoning 
by Veratrum album have been recorded; we know of none in the healthful adult 
from Veratrum viride. In the poisoning with Veratrum album, violent abdominal 
pain and diarrhoea are usually present; they are rare in poisoning with Veratrum 
viride. In our opinion, the medical practitioner who wishes to produce a profound 
influence with Veratrum viride should always order and see that he gets, not the 
veratrum of the U. S. P., but veratrum viride. 

Although the chemistry of veratrum is still in an unsatisfactory 
condition, there appear to be several alkaloids in it. Of these the 
most important are, jervine, rubijervine, -pseudo jer vine and proto- 
veratrine. The last named of these is by far the most toxic and at 
present appears to be the most important active principle. 

It should be noted that veratrine is not the active principle of 
veratrum, and bears no physiological relation to it. Although some 

* See N. Y. M. R., xxiv. 401. 

t Veratrum is retained in this chapter as our knowledge of its physiological action is somewhat 
in a state of chaos. It is probably not, however, in any proper sense of the word to be regarded as 
a cardiac depressant. 



CARDIAC DUPRKSSANTS 263 

ohemists have claimed to have obtained veratrine from veratrum, 
if present at all it is in such exceedingly small quantity as fco 
play absolutely no part in the physiological action of the drug. 

Official Preparations : 

Fluidextractum Veratri 1 to 3 minims (0.0G-0.2 C.c.). 

Tinctura Veratri (10 per cent.) 10 to 30 minims (0.6-2.0 C.c). 

Local Action. Veratrum viride is not actively irritant, although 
there is reason for believing that the vomiting which it causes is 
partly due to some local influence exerted by it upon the stomach. 
It yields its active principle very rapidly to absorption; its effects 
become apparent in fifteen to twenty-five minutes after its ingestion. 
Concerning its elimination we have no practical knowledge, but its 
active principle probably escapes through the urine. 

Physiological Action. — The only effect perceptible in man after 
the small physiological dose of veratrum viride is a reduction of the 
force of the pulse. If the dose has been a little larger the pulse fre- 
quency also falls very markedly, it may be to 40 or even 30 per minute. 
The volume of the pulse rises, though the force of it is very slight. 
The final reduction of the pulse-rate is accompanied by nausea, and 
at last by vomiting, which becomes after a very large dose exceedingly 
severe. By exercise this slow, large, soft pulse may be converted 
into a rapid, very feeble and small pulse. Under any circumstances 
the rapid pulse develops sooner or later if the dose has been sufficient, 
and is accompanied by intense muscular weakness and great sweating. 
Finally, there are a running, almost imperceptible pulse; a cold, 
clammy skin; intense nausea, and incessant attempts at vomiting, 
or retching, or hiccough; absolute muscular prostration; faintness; 
vertigo; loss of vision; and semi-unconsciousness. Various observers 
also speak of an excruciating precordial pain; but this we have not 
seen. The intestines are usually not disturbed, but severe purging 
has been noted. 

Circulation. — When a small dose of veratrum is introduced into 
the circulation it produces a remarkable slowing of the pulse with 
some fall of the blood-pressure. After toxic doses the pulse may 
become exceedingly rapid and the pressure rise to a point very much 
above the normal. The fall of the blood-pressure, seen after small 
doses, appears to be due solely to a slowing of the pulse, as H. C. 
Wood, Jr., has shown that, after section of the pneumogastric nerves, 
the pulse-rate is not decreased and the arterial pulse is elevated 
decidedly. The rise of pressure which occurs under these conditions 
appears to be due chiefly to a stimulant influence either upon the 
heart-muscle or the nervous mechanism regulating the heart's action, 
as it occurs after division of the spinal cord. The slowing of the 
pulse is due solely to stimulation of the cardio-inhibitory centres. 
The toxic increase in the pulse-rate appears to be brought about 
through paralysis of the peripheral endings of the pneumogastric 
nerve. 



264 



GENERAL REMEDIES 



In 1870, H. C. Wood made an elaborate study of the alkaloids jervine and 
veratroidine (rubijervine) in which he showed that jervine was a depressant to the 
respiratory centres to the respiration, to the vaso-motor centres, and to the heart- 
muscle; and the effect of the alkaloid upon the circulation is at least equally as well 
marked as its action upon the central nervous system. With jervine the chief action 
was a depressant action upon the nerve-centres, especially the respiratory centre. 
It is, however, also an active stimulant to the cardio-inhibitory centres, but its 
effect upon the cardiac muscle was comparatively slight, although, when given in 
extremely large doses, it exercised some depressant influence. 

In 1890, Salzburger separated two new alkaloids, one of which, protoveratrine, 
has been studied by Eden. It produces a primary slowing of the pulse with slight 
fall of blood -pressure, but the pressure soon rises to a point decidedly above the 
normal even although the pulse-rate may remain slow. The primary fall of the 




Fig. 14. — The Effect of Veratrdm on the Circulation. 

This shows that the fall of pressure caused by Veratrum is due solely to the slowing of the pulse, 
because the pressure rises above normal after section of the pneumogastric nerves. V — Injec- 
tion of Veratrum. X — Division of both pneumogastric nerves. Time marker indicates 2 seconds. 

pressure appears to be due to slowing of the pulse as it did not occur after division 
of the vagi. After large doses the pneumogastric nerves may later become paralyzed 
and there is produced a peculiar dyspnceic type of respiration and frequently con- 
vulsions. The rise of the pressure was found to occur also after division of the 
spinal cord and was therefore largely cardiac in origin. 

Nervous System. — In the frog, veratrum causes diminution of 
reflex activity and, in large enough dose, complete paralysis. These 
changes are probably due to an action on the spinal cord. 



SUMMARY.— Veratrum is a stimulant to the central cardio- 
inhibitory mechanism and probably also to the heart muscle, 
although the slowing' of the pulse generally produces a fall of 
the blood-pressure despite the stimulant influence upon the heart. 
It is also depressant to the motor side of the spinal cord. In 



CARDIAC DEPRESSANTS 265 

toxic doses it depresses the respiration, paralyzes the peripheral 
endings of the pneumogastrio nerve and, if given in large enough 
quantity, finally paralyzes the heart. 

Therapeutics. — Reasoning from fallacious ideas of its physio- 
logical action, veratrum has been, and still is, largely used in the 
treatment, of various sthenic inflammations, as pneumonia, peritonitis 
and the like, with the idea that through dilatation of the vessels it 
would relieve the congestion. As from more recent investigations it 
would appear that it does not dilate the vessels when given in thera- 
peutic dose, it is obvious that this use of the drug does not find a 
scientific justification. 

Veratrum is also used as a spinal depressant especially in eclamptic 
(•impulsions. It is recommended that for this purpose it should be 
given in full dose until the pulse-rate is reduced to about sixty a 
minute or less. 

Toxicology. — Overdoses of veratrum provoke vomiting so soon 
and so certainly that it is somewhat doubtful whether a robust 
adult could be killed by a single dose of any of its official prepara- 
tions, especially if prompt and judicious treatment were afforded. 

We have several times known a teaspoonful of its fluidextract to be taken, and 
Percy cites recoveries after the ingestion of a tumblerful of the tincture; after 
thirty grains of the resinoid; after two doses — a tumblerful each — of a syrup repre- 
senting a pound of the root to the pint. A feeble child, eighteen months old, was 
killed by thirty-five drops of the tincture, and a doubtful case of fatal poisoning in 
the adult is mentioned. J. D. Blake reports a death resulting from the administra- 
tion of between three and four drops of Norwood's tincture every two hours to a 
babe eleven months old; and a man convalescing from typhoid fever was killed 
by a drachm of the fluidextract.* 

In cases of poisoning, vomiting should be encouraged by large 
draughts of warm water until the stomach is well washed out. Then 
the patient should be forced to lie flat upon the back, with the head 
lower than the feet, and the efforts at vomiting should be restrained. 
If they cannot be checked, and if the prostration be severe, on no 
account should the patient be allowed to rise up, but must be made 
to vomit into a towel. A full dose of laudanum should be given by 
the rectum, and brandy or whisky be administered by the mouth. 
Tincture of digitalis and strychnine should be given hypodermically. 
We have noticed that spirits will sometimes be retained only when 
given undiluted, and in such form will quiet the stomach at once. 
If the stomach refuses alcohol in any shape, the rectum should be 
made use of. Ammonia may be employed as an adjuvant to alcohol. 
External heat is important, and mild flagellations, rubbing with 
coarse towels, sinapisms, etc., may be used to keep up the external 
capillary circulation. 

* Accounts of fatal cases mav be found in Am. J. Pharm., 1805; M. S. Rep., xl. 372- and 
P. M. T., xiv. 8G3. 



266 GENERAL REMEDIES 

VERATRINE. 

This alkaloid is procured from the seeds of Asagrasa officinalis 
(Veratrum Sebadilla*). As found in commerce, it is almost always 
more or less impure, and occurs as a grayish- white powder of an 
intensely acrid taste, and producing, even in the minutest quantity, 
when smelled, frequently repeated sneezing, which may continue 
for hours. 

Official Preparations : 

Veratrina J ff grain (2 Milligm.). 

Unguentum Veratrinse (4 per cent.) External use. 

Oleatum Veratrinse (2 per cent.) External use. 

Physiological Action. — Although veratrine is official it has no 
useful place in practical medicine, and we shall therefore only give a 
very brief outline of its physiological action. Locally it is intensely 
irritant to any surface with which it comes in contact, either skin or 
mucous membrane, and appears to have some local anesthetic effect 
also. Its most interesting action is its effect upon muscle. It affects 
the striated muscle tissue in such a way that the contraction follow- 
ing a single electrical shock, instead of relaxing immediately as in 
the normal condition, may require several seconds for complete 
relaxation. It appears also to have some depressant influence on both 
motor and sensory nerves. 

The only therapeutic use for which there is the slightest justifica- 
tion, is as a counter-irritant in neuralgia and allied conditions. The 
drug is actively toxic however, and presents no advantage over 
other counter-irritant remedies. 

ACONITE. 

The Aconitum Napellus,t or monkshood, is a tall perennial, indige- 
nous in Europe, and cultivated in this country for the sake of its spike 
of blue flowers. The leaves are three or four inches in diameter, and 
cut almost to the base into from three to seven three-lobed, wedge- 
shaped divisions. 

The root, which is the only official portion, is from three to four 
inches long, very tapering, about three-quarters of an inch in diameter 

* The action of sabadilline, the congeneric alkaloid of veratrine, has been partially studied by 
I. TJrpav (Montpellier Med., 1883, i. 274), who finds it to have only about one-twelfth the toxic 
power of veratrine. 

t All the species of the genus Aconitum are more or less poisonous, although A. Napellus is 
the only one official. For a study of the comparative strength of the various aconites, see Schroff 
{Journal fur Pharmacodynamik, 1857, 335). He arranges them as follows, commencing with the 
most virulent: A. ferox, A. napellus, with its varieties, neomontanum, tauricum, and variabile, 
A. cammarum, A. paniculatum, A. anthora. The toxic properties of A. anthora are very weak. 
Lycoctonine is the alkaloid of A. lycoctonum. For a physiological study of it by Ott, see Phila. 
Med. Times, vi. 25. 

Pseudaconitine, the alkaloid of Aconitum ferox, has been physiologically studied bv Boehm and 
Ewens (A. E. P. P., 1873, i.) and by Cash and Dunstan (P. Tr. R. S. L., Series B., 1902), who are 
in accord in finding that its physiological action is that of aconitine save only in regard to strength: 
0.4 grain of it is said to be equivalent in toxic power to 0.45 of true aconitine. Japaconitine, the 
alkaloid of Japanese aconite, Kuzauzu, A.japonicum, and A. fi scheri, according to Cash and Dunstan, 
acts physiologically as true aconitine, except that 0.85 grain is equivalent to 0.9 in toxicity. 

For local' application these three alkaloids may be substituted for aconitine. 



CARDIAC DEPRESSANTS 267 

at the base. Its taste is bitterish, acrid, and after a little while be- 
numbing, giving origin to intense tingling of the lips and mouth. It 
may be distinguished from horseradish root, with which it has been 
sometimes fatally confounded, by its external brown color and its 
lack of odor when scraped. The whole plant is active and tastes like 
the root. The U. S. Pharmacopoeia requires that the root shall con- 
tain not less than 0.5 per cent, of aconitine. 

In 1S;>;> Geiger and Hesse discovered in aconite the alkaloid 
aconitine. According to the most recent researches, there are in the 
root, however, besides aconitine, two alkaloids, benzaconine and 
aconine, which may also be made by the hydrolysis of aconitine, 
benzaconine being the isaconitine, and the principal constituents of the 
napelline and the picraconitine of older writers (Cash and Dunstan).* 

Aconitine occurs in colorless or whitish, odorless, rhombic tables 
or prisms. In extremely dilute solution it is capable of producing a 
characteristic tingling of the tongue or lips, but is so poisonous that 
it should never be tasted unless in solution of no greater strength 
than one part in five thousand, and even then with great caution. 
Amorphous aconitine of commerce is a more or less impure mixture, 
containing decomposition products. 

Official Preparations: 

Fluidextraetum Aconiti 1 to 2 minims (0.06-0.12 Co.). 

Tinctura Aconiti (10 per cent.) 5 to 15 minims (0.3-1.0 C.c). 

Aconitina ^foj grain (0.1G Milligm.). 

Physiological Action. — Local Action. — Aconite and aconitine are 
locally irritant, but this irritant influence is soon overwhelmed 
by the effect of the drug upon the peripheral ends of the sensory 
nerves, so that numbness and tingling are produced at the point of 
application. Moreover, the general influence of the drug is so over- 
whelming that the local effect counts for very little in practical 
medicine. 

Absorption and Elimination. — Aconite yields its alkaloids with 
great rapidity to absorption, and aconitine is capable of passing 
through the mucous membranes and even the skin, making it, in 
pure form, a dangerous external remedy. Concerning its elimination 
we have no knowledge. 

General Action. — The symptoms which are induced by small 
therapeutic doses of aconite in man are reduction of the force and 
frequency of the circulation, a sense of muscular inertia and weakness, 
and a slight tingling in the extremities or in the lips. If the dose 
administered is large, all these symptoms are intensified; the muscular 
weakness is extreme; the tingling is felt all over the body; the pulse 

* The activity of aconite depends chiefly upon the aconitine. According to Cash and Dunstan, 
benzaconine chiefly depresses the motor mechanism within the heart, also depresses the vaso-motor 
centre, causes slow pulse by vagal stimulation, and is the antagonist of digitalin. Aconine is so 
Feeble as to be disregarded in considering the effect of aconite. According to Cash and Dunstan, 
it has a curare-like action on the motor nerves, stimulates the roots of the vagi, strengthens the 
ventricular svstole, and does not affect the vaso-motor centres. 



268 GENERAL REMEDIES 

is feeble, and reduced to 30 or 40 per minute; the respirations are 
diminished; giddiness and disordered vision may be manifested, 
especially when the erect posture is assumed. After three or four 
hours these symptoms gradually subside. 

The symptoms produced by aconite in the lower animals are similar to those 
caused by it in man, the prominent manifestations being great disturbance of the 
respiration, muscular weakness, vascular depression, and finally death, with or with- 
out convulsions. As we have seen the rabbit after the injection of one-sixth or 
one-quarter grain of Morson's pure aconitine, the animal commences to jump ver- 
tically in a very peculiar manner, and often to squeal piteously. The jumping soon 
grows less and less powerful, and finally is replaced by severe convulsions, during 
which the animal often lies prostrate on its side. In the dog, however, the muscles 
have remained without a quiver during all stages of the poisoning; in the horse 
Harley has noticed convulsions. The convulsions are an inconstant symptom, 
dependent upon peculiarities of the individual or species, as well as upon the amount 
injected. Dilatation of the pupil frequently occurs, if it be not, indeed, a constant 
phenomenon. There is often severe vomiting. Death usually results from asphyxia, 
but if a large dose be given hypodermically, may occur in less than a minute, 
probably from sudden paralysis of the heart-muscle. 

Nervous System. — The mental condition in aconite-poisoning shows 
that the drug has no influence upon those portions of the cerebrum 
which are connected with consciousness and intellectuality. 

In the frog it abolishes reflex activity by paralyzing the peripheral 
sensory nerves. After larger doses there is probably also a depression 
of the motor side of the spinal cord. 

The persistence of voluntary movement after abolition of reflex actions, which 
was first noted by Boehm and Wartmann, and afterwards by Liegeois and Hottot, 
as well as by Mackenzie, proves that at a certain stage of the poisoning, while the 
motor pathway from the brain along the anterior columns and the efferent nerves 
is open, either the sensory nerves or the receptive centres of the cord are paralyzed. 

The discovery of Liegeois and Hottot — namely, that in the frog poisoned simul- 
taneously with aconite and strychnine there is a certain stage when no amount of 
irritation of the nerve will induce convulsion, while a slight direct irritation of the 
cord will cause violent strychnic spasms — seems to prove that at least the earliest 
abolition of the reflex activity is due to paralysis of the afferent nerve-fibres. In 
accord with this, Mackenzie found that when a nerve is protected from the poison 
by tying its supplying artery, irritation of it causes reflex actions when the remainder 
of the frog's periphery is insensible; that there is a stage of poisoning in which irri- 
tation of the extreme peripheral nerves fails to induce reflex movements, although 
such movements are called out by irritation of the sensory nerve-trunk; and that 
in the last stages of the poisoning irritation of the trunk is powerless, while irrita- 
tion of the posterior columns of the cord still produces wide-spread movements. 

In regard to the action of the drug upon the motor nerves the evidence is some- 
what contradictory. According to Achscharumow, when a frog is poisoned after 
the abdominal aorta has been tied, reflex and voluntary activity is preserved in the 
hind legs long after it has been lost in the anterior portion of the body; and, at 
the same time, while the brachial nerves, as tested by galvanic stimulation, have 
lost their power of transmitting impulses, the protected ischiatic nerves have pre- 
served their functional ability. P. C. Plugge confirms these statements, and also 
affirms that it is especially the peripheral ends of the motor nerves which are affected 
since when in the frog's leg the lower portion had been protected from the poison, 
galvanization of the nerve-trunk a considerable distance above the point of 
protection caused response in the tributary muscles. 



CARDIAC DEPRESSANTS 269 

These allegations would seem to prove that aconitine paralyzes the peripheral 
motor nerves, l>ut are directly contradicted by Boehm and Wartmann, by Liegeois 

and Hottot, by Mackenzie and by A. (iuillaud, who affirm thai. the nerves and 
muscles in poisoned animals preserve almost entirely their normal excitability until 
death, and that shutting otT access of the poison to the limb by tying does not affect 
the development of motor paralysis under the action of aconite. 

The explanation of this conflict of testimony is not to be found, as has been 
suggested by C. Ewers, in the use of different species of frogs, because Plugge em- 
ployed various species; nor is it in the employment of different commercial aconi- 
tines, because Plugge experimented with all the varieties, and found them to vary 
in power, but not in quality of action. Those observers who have found least in- 
fluence upon the motor nerves acknowledge some slight effect, and that when aconi- 
tine is brought in contact with an exposed nerve it rapidly destroys its functional 
activity; also that after death in the aconitized frog the motor nerves lose their 
irritability more rapidly than normal (Liegeois and Hottot, Guillaud, S. Ringer 
and H. Murrcll, Laborde and Duquesnel). 

From the evidence which lias been thus epitomized it seems to us that the 
most probable conclusion is that aconite exerts a feeble depressing influence upon 
the motor nerves. 

Spinal Cord. — Our knowledge of the action of aconite and its alkaloids upon 
the spinal cord is not complete; Boehm and Wartmann, Guillaud, Mackenzie, and 
(.'ash and Dunstan believe that after minute doses of aconitine there is, primarily, 
excitement or stimulation of the motor centres of the cord; Mackenzie affirms that 
the convulsions which are so severe in the frog after small quantities of aconite are 
chiefly of spinal origin, though he believes that the peripheral motor apparatus 
shares the motor stimulation. If the primary stimulation of the cord really occurs 
in mammals, it must be completely masked; at least we found in a series of experi- 
ments that when the spinal cord was cut in the mammal it was not possible to pro- 
duce aconitic convulsions in those portions of the body separated from cerebral 
influence, and no evidences of spinal excitement are ever seen in human poisoning. 
The conclusion of Boehm and Wartmann, that in the later stages of the poisoning 
there is depression of the motor side of the spinal cord, is probably correct, but so 
far as we know has never been actually proved. The preservation of voluntary 
movements in the poisoned frog after the abolition of sensation and of the reflexes 
shows that the motor paths from the brain to the cord through the muscle are pre- 
served at the time when the afferent apparatus is completely paralyzed, and that 
the action of aconite on the motor spinal cord is entirely subservient to its influence 
on the peripheral nerves. 

Muscles. — The early evidence in regard to the action of aconite 
upon the muscles was entirely contradictory, Wieland, Bucheim, and 
Eisenmenger affirming that the muscle-curve is much affected by 
the drug, Murray and Boehm and Wartmann that it remains unaffected. 
The researches of Cash and Dunstan seem, however, to prove that 
aconitine does not increase the irritability of the muscle-fibre, nor 
when given in moderate doses affect its capacity for work, though in 
some way it predisposes the muscle to asynchronism in the contraction 
of its bundles of fibres. 

Respiration. — Cash and Dunstan, having noticed primary increase 
of the rate of the respiration by aconitine, believe that the alkaloid 
acts primarily as a centric respiratory stimulant; but until it has been 
definitely proved that the amount of air forced in and out of the lungs 
is increased by aconitine, it must remain doubtful whether it ever has 
any true stimulant effect. When the poisoning is advanced the 
respirations in the mammal are slow, with a prolonged expiration 



270 GENERAL REMEDIES 

following immediately upon the inspiration. After the expiration 
there is a long pause, so that the whole breathing-cycle resembles 
very much that occurring after section of the vagi. The known 
influence of aconite upon the peripheral afferent nerves in general 
suggests that the poison disturbs respiration by paralyzing the 
peripheral afferent fibres of the vagi, but Mackenzie states that in 
the aconitized animal section of the vagi produces no effect on the 
respiration; and Boehm and Wartmann affirm that aconite produces 
its usual effect after division of the vagi. It is plain that even if the 
aconite does paralyze the peripheral afferent vagi it must also act 
upon the respiratory centres, since arrest of respiration could not be 
caused by afferent palsy. As the arrest occurs in the frog before the 
motor nerves are affected by the poison, Liegeois and Hottot believe 
that the disturbance is centric; and we think there can be no doubt 
that aconite is a direct depressant and paralyzant of the respiratory centres. 

Circulation.- — The effects of aconite on the circulation are complex 
and the changes produced by toxic doses not clearly understood. 
It produces first a slowing of the pulse with a fall in the blood-pressure. 
The slowing of the pulse is due chiefly to stimulation of the cardio- 
inhibitory centres, although there is some evidence that the drug 
affects also the peripheral endings of the pneumogastric nerve. The 
fall of pressure seems to be due entirely to the changes in the heart, 
there being a direct depressant action upon the cardiac muscle. The 
vaso-motor system does not seem to be affected by therapeutic doses. 

After toxic doses the pulse becomes more rapid than normal — 
probably through paralysis of inhibition perhaps from a direct action 
on the heart itself. Later the rhythm of the heart is seriously affected, 
the contractions of both auricle and ventricle being very unequal, 
and the normal auricular and ventricular rhythm seriously impaired 
(see S. A. Matthews, also J. T. Cash and W. R. Dunstan). The intra- 
ventricular pressure also varies greatly, and the whole action of the 
heart is in such a state of confusion as most seriously to interfere 
with the coronary supply and the general mechanism of the circulation. 
After death the cardiac muscle fails to respond to galvanic irritation.* 

In some experiments a brief rise of pressure has preceded the fall (Boehm and 
Wartmann, Laborde, Duquesnel). It is probable, however, that this rise of pressure 
is secondary, and not directly caused by the poison. Very early the blood-pressure 
begins to fall; after a time the fall becomes pronounced, and the pulse, which has 
been at first slowed, grows rapid. Then what is known by some observers as the 
characteristic condition develops, consisting especially of great and rapid fluctua- 
tions of pressure, which may in the dog amount to fifty millimetres of mercury, 
and may for the moment even carry the pressure to a higher than the normal point. 
The pulse finally becomes extremely rapid and irregular; the heart is in a condition 
of delirium, and soon stops in diastole. 

In endeavoring to elucidate the cause of the cardiac phenomena of aconite- 
poisoning it is evident in the first place, that aconite affects the heart directly. 

* According to S. A. Matthews, during the period of delirium of the ventricle the auricle can 
generally be restored to regular contraction by cutting one of the big veins and allowing it to free 
itself of the contents. 



CARDIAC DEPRESSANTS 271 

Achscharumow affirms thai aconitine acts upon the Erog's heart, removed from the 
body, as ii docs upon the heart of the normal batraohian. Liegeois and 1 1 < > 1 1 • > r 

have produced the ordinary cardiac phenomena of aconite-poisoning by placing 
I lie alkaloid upon the heart. 

The first question thai offers itself is as to the cause of the primary .slow pulse. 

The concordance of recent investigators warrants the conclusion that aconite 
primarily slows the heart, by stimulating inhibition; the stimulation being chiefly 
centric, lmt, if the experiments of Matthews be correct, also in a measure 
peripheral. 

Boehm and Wartmann affirm that the development of the slow pulse is not 
prevented by the previous section of the vagi or by atropinization. Achscharumow, 
however, states that section of the vagi performed during the early stage of aconite- 
poisoning is followed by a pronounced immediate rise both in the number of the 
cardiac pulsations and in the arterial pressure. Lewin affirms the correctness of this, 
but states that the rise is of very brief duration, and is soon followed by the usual 
reduction. S. A. Matthews states, however, that after section of the vagi aconite 
reduces t lie heart's rate to a slight extent only, and that even this reduction is 
entirely prevented by the administration of atropine. Cash and Dunstan affirm 
that section of the vagi in the period of slow pulse from aconite is followed by an 
immediate increase of the rapidity of the beat. 

The rapid pulse of the advanced stages of aconite-poisoning is attributed by 
S. A. Matthews chiefly to the ever-increasing irritability of the cardiac muscle 
under the action of aconitine, and to us seems to be in part due to the action of the 
alkaloids upon the heart-muscle, and to be also in part the outcome of depression 
of the peripheral vagi. 

The evidence given by different experimenters in regard to the condition of the 
peripheral vagi in aconite-poisoning is somewhat contradictory. Boehm and Wart- 
mann, and Plugge, affirm the existence of vagal paralysis. S. A. Matthews says 
that "the peripheral inhibitory mechanism is not paralyzed by the aconitine during 
the irregular stage, as is generally stated;" but we have no doubt as to the accuracy 
of the assertion of Cash and Dunstan, that, although when the dose of aconitine has 
been so large as to be rapidly lethal the vagal terminations may not be completely 
paralyzed up to death, when small lethal doses have been used, complete peripheral 
vagal paralysis may develop, or a condition appear, also noted by Boehm, in which 
the vagi may respond one minute to stimulation and refuse to respond the next. 

Our knowledge of the action of aconitine upon the vaso-motor system is not 
complete. The paralysis of the afferent nerves in advanced aconite-poisoning, 
by shutting off from the vaso-motor centre the impulses which normally reach it 
from without, must certainly affect the general tone of the vessels, a reasoning 
which finds strong confirmation in the fact asserted by Boehm and Wartmann, that 
there is a stage in aconite-poisoning in which galvanization of a sensitive nerve 
does not produce rise of the arterial pressure, which, however, is developed at once 
when the vaso-motor centres in the medulla are stimulated. 

S. A. Matthews and Cash and Dunstan affirm that the first action of the drug 
upon the vaso-motor centre is as a stimulant, but we have not been able to find 
in their papers any sufficient proof of this, and do not believe that the conclusion is 
probable. It is likely that in the advanced stages of the poisoning the vaso-motor 
centre is depressed or paralyzed, though this has not been positively proved. The 
best evidence is that furnished by Cash and Dunstan, — namely, that there is a 
I>eriod in which mechanical asphyxia ceases to elevate the pressure. 

That the efferent vaso-motor apparatus is not paralyzed is shown by the facts 
i hat in advanced poisoning galvanization of the sympathetics in the neck causes 
contraction of the vessels (Nunneley), and that the splanchnies retain almost to 
the last their functional activity. 

Temperature. — In the very beginning of aconite-poisoning the 
bodily temperature may rise slightly, but in severe poisoning a very 
pronounced fall occurs. The reduction of the bodily heat is probably 



272 GENERAL REMEDIES 

caused by an increase of heat-dissipation. If vaso-motor paralysis 
occurs in aconite-poisoning it will account for this loss of heat. Fur- 
ther, it is entirely possible that aconite, without producing vaso- 
motor paralysis, may, by destroying the conducting power of the 
afferent nerves, put an end to the automatic relation between heat- 
production and heat-dissipation. In accord with this is the observation 
of Brunton and Cash, that in animals exposed to a high temperature, 
aconite, far from depressing the temperature, favors its increase, 
while when the animal is exposed to cold, aconite accelerates the fall 
of the bodily heat remarkably (confirmed by Cash and Dunstan). 

SUMMARY.— Locally, aconite is slightly irritant at first and 
subsequently paralyzant especially to the sensory nerves. It yields 
its active principle rapidly to absorption. Aconite has little direct 
action upon the cerebrum, unless it be upon the perceptive centres 
of general sensibility, concerning -which there is still dispute. It 
is asserted by some authorities that the small dose stimulates 
respiration, but this has not been proved. In toxic dose it acts 
as a powerful depressant to the respiratory centres, and usually 
kills by centric paralytic arrest of respiration. It also paralyzes 
the peripheral fibres of the vagus in the lungs, and thereby not- 
ably affects respiratory rhythm. Its action upon the spinal cord 
remains uncertain, some authorities believing that it primarily 
stimulates the motor side of the cord, and very late in the poi- 
soning causes centric motor depression. Its dominant influence, 
so far as the nervous system is concerned, is, however, upon the 
sensory nerves, affecting primarily their peripheral filaments and 
involving later their trunks. It has also some, but a much less 
powerful, depressive action upon the motor nerves. According to 
some authorities, the stage of nerve-paralysis is preceded by one 
of nerve-stimulation, but this is extremely doubtful. 

Aconite reduces very markedly the rate of the pulse and the 
arterial pressure, the primary stage of slow pulse being followed 
by one of rapid irregular pulse, with very fluctuating but still 
low pressure. The chief cause of the slow pulse is stimulation 
of the vagal nerve (aconitine, benzaconine), which is followed, 
when the rapid pulse comes on, by depression of the peripheral 
vagi. The rapid pulse is in part due to the withdrawal of inhibi- 
tion, and probably also in part to a direct action of aconitine 
upon the muscle-irritability. Aconitine appears primarily not to 
affect the muscular strength of the heart, but on account of the 
depressing influence of the benzaconine upon the muscle the 
cardiac force is weakened by aconite from the beginning. 

The action of the drug upon the vaso-motor system is not 
established; several recent observers affirm that the first action 
of the drug upon the vaso-motor centre is stimulation, which 
seems to us to be unproved and improbable; in the advanced 
stages of the poisoning the vaso-motor centre is probably depressed 
or paralyzed, but even concerning this our knowledge is uncer- 
tain. The efferent vaso-motor nerves are not affected. 

The bodily temperature is reduced by aconite by an increase 
of heat-dissipation, and perhaps also by an action on the thermo- 
genetic nervous system. On the glandular system of the body, 
except that of the skin, aconite has little or no influence. 



CARDIAC DKI'RKSSANTS 273 

Therapeutics. — The general indication for the use of aconite is t<> 
lower arterial action, but the selection of this drug among other 
cardiac depressants for this purpose should be governed by certain 
definite principles, depending upon the known peculiarities of its 
action. When the high arterial pressure is chiefly cardiac in origin, 
it is the best drug of its class, having in therapeutic dose little or no 
influence upon the system other than upon the heart, and producing 
DO disturbance of gastric or intestinal digestion. No cases, or reports 
of cases, of cumulative effects parallel to those caused by digitalis 
have come under our notice, but when small doses are given con- 
tinuously there is a progressive increase of effect. In cases of cardiac 
hypertrophy, or when there is in valvular disease excessive compensa- 
tion, aconite is the best remedy that we have. Given in doses of the 
tincture, from two to five minims (0.12-0.3 C.c.) three times a day, 
it acts steadily and persistently. When the administration is free, 
the effect should always be watched carefully and the dose lessened 
pro re nata. 

On the other hand, when a sudden, very powerful influence to meet 
an emergency is desired, and especially when it is necessary if possible 
to produce wide-spread vaso-motor weakness and consequent relaxa- 
tion of the blood-vessels, aconite should not be employed. The 
overdose is more likely to produce serious results than is the overdose 
of veratrum. 

In irritative fevers, as the ephemera of childhood from gastro- 
intestinal irritation or other cause, aconite in moderate dose often 
acts most happily. Especially is it useful in combination with other 
drugs which have a tendency to increase the secretion from the skin, 
when it is desired to produce free sweating. If only a moderate but 
continuous skin effect is desired, aconite may be given with the 
solution of potassium citrate; to it may be added, if circumstances 
favor, antipyrine. When it is desired, as in acute muscular rheumatism 
or in a forming grippe, to produce very free sweating, a combination 
of aconite, pilocarpine, and antipyrine is very effective. In urethral 
fever due to the passage of the catheter or bougie, aconite often acts 
most happily. 

A second indication which aconite might be used to fulfil is to 
allay spasm. As, however, its influence upon the motor centres and 
nerves is much less than upon the sensitive centres and nerves and 
upon the heart, the indication is better met by other remedies. 

A third indication, which it would seem from its known physio- 
logical action that aconite should meet, is to relieve over-excitation of 
the sensitive nerves. Although aconite was formerly very much used 
for the relief of pains which were called neuralgic, and is sometimes 
useful when an acute neuritis has followed exposure to cold, and is 
of a rheumatic type, it is rarely of real service even as a local remedy, 
and is of no value whatsoever in such diseases as migraine when the 
pain is of centric origin. 
18 



274 GENERAL REMEDIES 

Given in full doses in the reflex vomiting of pregnancy, aconite is 
often advantageous, acting probably by benumbing the sensory 
reflex centres, or possibly the afferent peripheral gastric nerves. We 
have noticed that relief lasts only so long as decided constitutional 
effects from the drug are apparent. 

Toxicology. — When a poisonous dose of aconite has been ingested, 
the first thing noticed in most cases is a burning or tingling in the 
throat or in the extremities, soon spreading over the whole body. 
The pulse rapidly falls in frequency, and in a very little time becomes 
exceedingly weak, intermittent, irregular, and finally imperceptible; 
the muscular strength is greatly reduced and sometimes almost 
entirely gone; the respirations are shallow, feeble, irregular, and 
infrequent; the general sensibility is very much benumbed, so that 
marked anesthesia of the surface is present; the skin is bedewed with 
cold sweat; the countenance is anxious, sunken, livid, and the eyes 
are often protruded, or are even spoken of as glaring; the pupil is 
generally dilated, but when there are no convulsions may be con- 
tracted; gastric burning is sometimes complained of, and severe 
vomiting may be present, but the stomach is not rarely retentive. 
The intellect generally remains unaffected until very near the close, 
sometimes to the very moment of death. In the collapse of the latter 
stages of aconite-poisoning the special senses may be lost, especially 
the sight. The voice is very generally extinguished. Convulsions 
occur in some cases, not in others; and certainly in some instances, 
if not always, the patient is unconscious during their continuance. 
Diplopia, or other disorder of vision, has been noted in some cases. 
Death may occur suddenly, especially directly after some exertion on 
the part of the patient, from syncope. 

The symptoms usually come on in a very few minutes. In the 
shortest case we have met with, death occurred in thirty minutes. 
The average time (Reichert) is three and a third hours, the longest 
recorded case being five and a half hours. Five grains of an extract 
and eighty minims of a tincture are said to have caused death (Reichert). 

The aconitines of commerce vary inordinately in strength, so that while one- 
sixteenth of a grain (prepared by Petit,* of Paris) caused the death of Carl Meyer 
in five hours, and a quarter of a milligramme is said to have produced violent poison- 
ing, several grains of the impure article so largely sold have been recovered from. 
The symptoms have been in general those of aconite-poisoning, but excessively 
violent pains and convulsions have been very marked features of some of the cases. 
(For discussion of aconitine-poisoning, see Thomas Stevenson, M. Jules Bassott, 
also six cases, Lhote and Vibert.) 

The only diagnostic symptom of aconite-poisoning is the peculiar 
tingling, which is probably always present, though in suicidal cases the 

* The best discussions of the relative strength of these alkaloids that we know of may be found 
in Schmidt's Jahrb., ccii. 124, and in Des Aconits, by J. V. Laborde and H. Duquesnel, Paris, 1883. 
Lohte and Vibert (Annal. d'Hyg. Publ., 1892, xxviii.) assert that the crystallized aconitine of 
Duquesnel is an essentially different poison from the amorphous aconitine of commerce or from 
the aconitine sulphate of Merck. The latter in the isolated frog's heart they found to produce 
gradual progressive enfeeblement, while the Duquesnel aconitine caused primarily great increase 
in the size of the cardiac pulsation, with periods of ataxia, followed by depression. 



CARDIAC DEPRESSANTS 275 

patient may refuse to reveal it, or in advanced poisoning uncon- 
aciousness may prevent its being told. The presence in any case 
known to be one of poisoning of absolute prostration with almost com- 
plete failure of the pulse, great muscular relaxation, and other symp- 
toms of collapse, without vomiting, purging, or any disorder of the 
pupil or other toxic manifestations, is sufficient for a working diagnosis. 
The first indication for treatment in aconite-poisoning is evacua- 
tion of the stomach; as emetics usually fail, on account of the local 
gastric anesthesia, the stomach-pump may often be used, but the 
danger of causing fatal collapse in extreme cases must not be over- 
looked. Tannic acid may be administered as an imperfect antidote. 
Hot concentrated alcoholic stimulants should be freely given; strych- 
nine, atropine, and digitalis* should be used hypodermically with 
great boldness, tempered with caution. Ammonia may be injected 
into the veins, if it be found practicable. The patient must be kept 
upon the back, with the feet a little higher than the head, and external 
heat be used freely to maintain temperature. Laborde and Duquesnel 
affirm that in the lower animals death after a usually fatal dose of acon- 
itine can be prevented by artificial respiration; and in a case of human 
poisoning, if the heart's action were at all sustained, and the respira- 
tion failing, Sylvester's method or forced artificial respiration might 
be resorted to. 

HYDROCYANIC ACID. 

Pure hydrocyanic acidf or prussic acid (HCN) is a colorless, 
transparent, volatile, inflammable liquid, giving rise to giddiness and 
headache when smelled, and having, it is said, a burning, bitter taste. 
So poisonous is it that when inhaled it causes death, and it must be 
handled with the greatest caution: smelling and tasting it are exces- 
sively dangerous proceedings. It is, indeed, an imperative rule that 
no one should experiment with anhydrous prussic acid alone, or 
under any circumstances in summer, or in a warm room, or in an 
apartment whose open windows and doors do not admit of a free 
draught of air. The chemist Scheele, the discoverer of prussic acid, 
is believed to have been killed by the inhalation of the fumes of this 
material, whose poisonous properties were first pointed out by the 
Berlin apothecary Schrader in 1803. The anhydrous acid is soluble in 
water and in alcohol, but is never kept in the shops, and is not official. 

* The original discovery of J. Milner Fothergill (Digitalis, London, 1871, 6), that digitalis is 
the cardiac antagonist of aconite, has been abundantly confirmed. The careful work of Matthews 
and of Cash and Dunstan has demonstrated that it is benzaconine which is especially antagonized 
by the digitalis, atropine being the cardiac antagonist of aconitine. Clinical experience, although 
still limited in extent, strongly corroborates the experimental evidence of the value of digitalis. 
Successful cases may be found in Brit. Med. Journ., Dec. 11, 1872 (f3i Fleming's tincture, Tinct. 
digitalis lT\x hypodermically); Bost. Med. and Surg. Journ., Oct. 1879, 544 (foiii Tinct. aconit. 
rad., Tinct. digitalis lT)lx hypodermically); Indian Med. Gaz., xvii. 323 (Aconitum ferox root forty- 
eight grains, Tinct. digitalis Hlxxv hypodermically and foi by mouth); Phila. Med. Times, xiii. 
328. Ammonia injections were unsuccessful in a case reported in the Australian Med. Journ., 
1879, i. 283. G. H. Tuttle (Boston Med. and Surg. Journ., 1891, exxv.) has reported recovery after 
seven and a half drachms of the tincture, under the free hypodermic use of brandy and digitalis, 
the same remedies with tincture of nux vomica being given internally, and auxiliary measures used. 

t Cyanogen Gas has been studied physiologically by B. Bunge. He finds that it kills by paralyz- 
ing the centres of respiration, but that it is less powerful in its influence than is hydrocyanic acid, 
and causes only very feeble convulsions. 



276 GENERAL REMEDIES 

Hydrocyanic acid of common medical parlance is the official 
Diluted Hydrocyanic Acid, a colorless, watery solution, containing 
two per cent, by weight of the anhydrous acid. Its odor and taste 
are the familiar ones of peach-kernels and bitter almonds; its reaction 
is faintly acid. As it has a great tendency to undergo spontaneous 
decomposition, especially under the influence of light, it should be 
kept in well-stoppered, dark-colored bottles. 

Potassium Cyanide occurs in white, amorphous, opaque masses, 
or as a granular powder, odorless when dry, but deliquescing in the 
air and exhaling the odor of prussic acid. It is readily soluble in water. 

Official Preparations : 

Acidum Hydrocyanicum Dilutum (2 per 

cent.) 1 to 3 minims (0.06-0.18 C.c.;. 

Potassii Cyanidum ^ to ^ grain (5 to 6 Milligm.). 

Argenti Cyanidum Not used internally. 

Local Action. — Absorption and Elimination. — Hydrocyanic acid 
appears to be free from irritant properties, but is a universal depres- 
sant poison, capable, when in sufficient amount, of paralyzing all 
higher tissues, and having, when applied locally, an especially powerful 
influence upon sensory nerve-endings. It is absorbed with almost 
instantaneous rapidity through all mucous membranes. Concerning 
its fate in the body we have no knowledge except that it is either 
destroyed or eliminated with the greatest rapidity, so that its action 
is extremely fugacious. 

General Action. — The symptoms produced by prussic acid in man 
are so rapid in development and course that usually the patient is 
dead or convalescent before seen by the physician. The ordinary 
therapeutic dose produces no distinct manifestations; after the toxic 
dose the symptoms come on suddenly. In a moment or two the 
individual falls to the ground insensible and convulsed, the respira- 
tions arrested or occurring at long intervals, the eyes salient, the pupil 
dilated, the mouth covered with bloody froth. If the dose be suffi- 
ciently large, death may occur in three or four minutes; if less has 
been taken, deep insensibility, tetanic or clonic convulsions, dilated 
pupils, a bloated countenance, c.yanosed surface, set jaws, and irregular 
respiration constitute the chief symptoms. The breathing is mostly 
convulsive, with deep, forcible expirations, but in some cases it has 
been stertorous. Death results from asphyxia. After small toxic 
but not lethal doses of prussic acid, giddiness, lightness of the head, 
nausea, a quick pulse, and muscular weakness are the chief symptoms. 

After a full dose of absolute hydrocyanic acid, the lower animal gasps once 
or twice, and then instantly falls in a tetanic or clonic convulsion, or else drops 
motionless and powerless upon its side, heart and lungs ceasing almost at once. 
After a smaller toxic dose the signs of asphyxia at once manifest themselves, and 
grow more and more intense, until they end in total arrest of respiration. The 
heart beats irregularly, often at first slowly and strongly, with intervals of suspension 
of movement, but always becoming weaker and more rapid in its action, until, after 
the breathing has ceased, its efforts gradually die away. Ordinarily, three distinct 



CARDIAC DEPRESSANTS 277 

stages are apparent: a Brat, very brief one, of difficult respiration, slow cardiac 
action, and disturbed cerebration; a second, convulsive Stage, with dilated pupils, 
violent convulsions, unconsciousness, loud cries, vomiting, often spasmodic urina- 
tion and defecation, erections, etc; and a third period, of asphyxia, collapse, and 
paralysis, sometimes interrupted by partial or even general spasms. 

The slow form of the poisoning follows the exhibition of the poison in an amount 
just sufficient to kill. After the ingestion of such a dose, no phenomena are offered 
for some seconds; then the breathing becomes labored and the pulse slow and full. 
The animal perhaps erics out, and muscular tremblings rapidly grow into clonic 
and tonic convulsions, which continue at intervals until the third stage — that of 
collapse — is developed. When the third stage is developed, the anesthesia is marked, 
affecting first the hind legs, but finally spreading to all parts of the body, and even 
being complete in the widely dilated pupil. Death finally results from failure of 
respiration. Recovery may occur even after the conjunctiva has lost its sensibility; 
the return to life by a subsidence of the symptoms is usually rapid, so that generally 
in from one-half to three-quarters of an hour the animal will be eating as though 
nothing had happened. Coullon, however, noted persistence of paralysis, in some 
cases, for days. 

Blood. — When prussic acid is added to blood outside of the body 
it produces a new chemical compound known as cyanohemoglobin. 
Whether this substance is produced in the body or not is somewhat 
questionable. During life, however, it has been shown by numerous 
observers that in early stages of poisoning the blood in both arteries 
and veins has a bright arterial hue and in the later stages, if death has 
not occurred too rapidly, a deep venous hue. The last change is 
due to the failure of respiration. The occurrence of bright red 
blood in the veins, however, has not as yet been satisfactorily 
explained. 

F. B. Vietz, E. L. Schubarth, J. F. Sobernheim, Coze, and Claude Bernard, 
have demonstrated the occurrence of the phenomena of red blood in the veins. 

According to Gaethgens, the scarlet venous blood of the first stage of the poison- 
ing shows clearly the absorption bands of oxyhemoglobin under the spectroscope, 
while Preyer has demonstrated that the dark blood of the advanced stages of the 
poisoning gives only the lines of reduced hemoglobin. 

As was first shown by W. Preyer, and subsequently confirmed by Carl Gaeth- 
gens, directly after the administration of the poison, in the mammal the venous 
blood becomes almost immediately of a bright arterial hue, which, however, rapidly 
darkens until all the blood of the body is venous. If the mammal dies suddenly 
from cardiac paralysis during the first stage of the poisoning, this excessive arterial- 
ization may be found after death, and in cold-blooded animals, the bright color 
persists for many hours (Preyer). If, however, life is more prolonged, the blood 
grows dark. 

The explanation offered by Hoppe-Seyler that the drug produced a functional 
paralysis of the red blood-corpuscles seems improbable, in view of the fact of the 
later occurrence of the reduction of the oxyhemoglobin. Gaethgens has shown, 
however, that during the stage of red blood there is diminished elimination of car- 
bonic acid from the lungs. There is, however, formed no new chemical compound in 
the blood, as is shown by the spectroscopic examinations of Preyer, Laschkewitsch, 
and Hiller and Wagner, and also by the fact, determined by Lecorche and Meu- 
riot, that in the stage of venous blood artificial respiration would restore oxyhemo- 
globin. It would seem, therefore, that the drug in some way, perhaps by its effect 
upon the tissues rather than upon the blood, prevents the giving up of oxygen by 
the red blood-corpuscles. When the dose has been large enough to cause sudden 
death the bright red hue may persist for some time after death. 



278 GENERAL REMEDIES 

As first discovered by Hoppe-Seyler, and afterwards confirmed by Preyer, 
when hydrocyanic acid is added to blood outside of the body there is produced a 
new substance giving rise to new spectroscopic lines and without ozonizing power, 
the so-called cyanohemoglobin. 

Alterations in the form of the corpuscles of the blood have been suggested as 
the cause of the changes of the color, Ernst Geinitz having found that, both in the 
frog and in the mammal, prussic acid distorts the blood-corpuscles. On the other 
hand, in the observations of Preyer, although such alteration of the blood-corpuscles 
could be produced in mammalian blood outside of the body, yet in blood drawn 
immediately after death from prussic acid the corpuscles offered their usual char- 
acter; a fact confirmed by Hiinefeld.* 

Whatever may be the cause of the changes in the blood, the experiments of 
Lewisson would appear to prove that the action of the poison on the nervous system 
is a direct one, and not due to these changes in the vital fluid, for the observer men- 
tioned found that prussic acid acted upon the bloodless "salt frog" as upon the 
normal batrachian. 

Circulation. — When a moderately large dose of prussic acid is 
injected into a vein there occurs a marked but fugacious rise of the 
blood-pressure with slowing of the pulse, followed by a fall of the 
pressure below the normal and later an extremely rapid pulse. Ac- 
cording to Preyer, Laschkewitsch and Lecorche and Meuriot, 
hydrocyanic acid is a depressant to the heart-muscle and the primary 
rise of pressure which occurs is, therefore, due probably to a temporary 
stimulation of the vaso-motor centres. These latter are afterwards 
paralyzed, as Lazarski has found that galvanization of the sensitive 
nerve in the late stages of poisoning will not cause a rise of pressure. 
Lazarski has also found that the slowing of the pulse caused by mod- 
erate doses of hydrocyanic acid is prevented by previous section of 
the vagi and it may therefore be considered that the drug is stimulant 
to the cardio-inhibitory centres. According to Boehm and Knie, 
however, the late slowing of the pulse from toxic doses is not affected 
by vagal section and is probably due to direct action upon the cardiac 
muscle or its intrinsic ganglia. 

Respiration. — Hydrocyanic acid acts directly upon the respiratory 
centres as a depressant, so that in poisoning by it the respiratory 
movements are lessened from the beginning, and becoming more 
and more distant finally cease before the heart's action is arrested. 

Preyer found that, after division of the vagi, normally lethal doses did not kill, 
and that when death was brought about by the exhibition of larger doses it was by 
cardiac arrest. From this he deduces the conclusion that the prime respiratory 
action of the poison is upon the peripheral ends of the vagi. Preyer 's experiments 
have been partially confirmed by Lecorche and Meuriot; but Boehm and Knie 
have in a series of experiments found that section of the vagus has no influence 
upon the respiratory action of the poison, and in this have been confirmed by Jos. 
Lazarski. Even if investigations had proved the correctness of Preyer's experi- 
ments, his conclusion could not be considered established, because we know so 

* According to E. Ray Lankester (Pfliiger's Archiv, 1869, 492), when blood is shaken with 
cyanogen gas, and allowed to stand for two or three hours, the spectrum-changes are exactly the 
same as after similar treatment of blood with CO. The compound of cyanogen and hematin (Cy.Hb) 
offers not only the identical spectrum of CO.Hb, but also, like the latter, is unaffected by reducing 
agents. After the blood stands awhile, according to Lankester, the spectrum of hydrocyanic acid 
(H,CN) becomes visible in it, and the Cy.Hb undergoes conversion into the cyanohemoglobin 
(Cy.Hb) of Hoppe-Seyler. 



CARDIAC DEPRESSANTS 279 

Imperfectly the normal relations of the pneumogastrics to respiration. Moreover, 
Joseph Jones found that while to kill an alligator by I lie administration of prussic, 

acid required a considerable length of time, its application to the medulla produced 

within one minute a most powerful expiration, ending in permanent contraction of 
the muscles of respiration and collapse of the lung. In the experiments of H. Ha- 
yashi and K. Muto doses of 15 milligrammes per kilogramme of potassium cyanide 
caused, in the rabbit, fatal paralysis of respiration at a time when the phrenic and 
motor nerves were still excitable. 

Nervous System. — Hydrocyanic acid produces in the frog a con- 
dition of complete paralysis in which Kolliker believes that first the 
brain and next the reflex centres of the spinal cord are affected, 
although he has demonstrated, as have Funke and Stannius, that the 
motor nerves and the muscles are both finally paralyzed by the drug. 
Kolliker has also shown that, when applied locally, the drug paralyzes 
the peripheral endings of the sensory nerves. 

It is a question of interest to decide as to the cause of the convul- 
sions in poisoning by hydrocyanic acid. We have found that they 
do not occur after section of the cord in parts below the point of sec- 
tion, and that they are therefore cerebral in origin. It is probable 
that the convulsions are secondary, asphyxial, or due to disturbance 
of circulation. Laschkewitsch, who opened the thorax of a rabbit so 
as to expose the heart, maintained artificial respiration, and admin- 
istered prussic acid; directly after arrest of the heart had commenced 
the convulsions came on; also in the earlier observation of Coze, 
the convulsions did not occur until directly after the arrest of the 
circulation. In frogs poisoned with hydrocyanic acid, convulsions 
do not take place. Preyer states that after section of the vagi con- 
vulsions do not generally happen in mammals, but if artificial 
respiration be performed they come on. 

SUMMARY. — When in sufficient concentration hydrocyanic acid 
is a powerful depressant poison to all the higher tissues. It is 
absorbed immediately, and acts at once, but its influence is over 
in a few minutes. In poisoning' by it death usually occurs through 
centric paralysis of the respiration, but the depression of the 
heart's action is pronounced, and diastolic cardiac arrest some- 
times takes place simultaneously with or even before cessation 
of breathing. It first stimulates, then paralyzes the vagi; it first 
stimulates, afterwards paralyzes the vaso-motor system. Upon 
the nerve-centres it has a most pronounced depressing influence, 
and it is also a paralyzant to the nerve-trunks and to the mus- 
cles themselves. There is some reason for suspecting that after 
the small toxic dose of hydrocyanic acid the paralytic stage is 
preceded by a very brief stage of excitement, with centric in- 
crease of the respiratory activity, rise of the arterial pressure 
(caused by an influence upon the vaso-motor centres and perhaps 
upon the heart) , and slowing of the pulse from stimulation of the 
cardiac inhibitory centres. Outside of the body hydrocyanic 
acid attacks the red blood-corpuscles, forming a new compound, 
cyanohemoglobin ; but the occurrence of this change during life 
in hydrocyanic-acid poisoning is doubtful. 



280 GENERAL REMEDIES 

Therapeutics. — Our knowledge of the physiological action of 
prussic acid does not lead to a belief in its wide applicability to the 
relief of disease, and we think that clinical experience has demon- 
strated that it is of little value except in meeting three indications: 
first, to allay cough; second, to relieve irritation of the gastric nerves; 
third, to allay irritation of the peripheral sensitive nerves. 

Prussic acid has been used very largely to allay cough, either itself 
or in the form of potassium cyanide. Owing to the extreme fugacious- 
ness of its action, it is, however, of very little real value for this pur- 
pose. It is improbable that the effect of a therapeutic dose of the acid 
lasts over twenty minutes, or of the cyanide over forty-five minutes. 

There can be, on the other hand, no doubt as to the value of 
prussic acid in certain stomachic affections, especially nervous vomit- 
ing and gastralgia. When the pain is accompanied by decided dys- 
peptic symptoms the remedy will sometimes succeed, but more often 
fails. Even in the most favorable cases it does not always afford 
relief; and as the relief when it does occur is immediate, or at least 
is very soon apparent, it is useless to persist long in the exhibition of 
the remedy. In these cases its action is probably local, as it certainly 
is when the acid is employed to relieve itching in prurigo and other 
cutaneous diseases. For this purpose it is used as a wash (one-half 
to one fluidrachm in one fluidounce) ; but great care must be taken 
to avoid constitutional effects, especially when there is any abrasion 
of the skin. Very serious results are said to have been caused by its 
absorption when carelessly used in skin diseases. 

Prussic acid has been commended as an arterial sedative; but 
unless given in dangerous doses it has no such action. 

Toxicology. — The symptoms of prussic-acid poisoning have 
already been mentioned (p. 276): those of most value from a diag- 
nostic point of view are the sudden occurrence of unconsciousness, 
the violent convulsions, the general paralysis, the peculiar character 
of the breathing, expiration being prolonged and forced, and the 
rapid results. The odor of prussic acid upon the breath is very often, 
but by no means always, present. When distinct, it is, of course, of 
great diagnostic value. Leaving out of sight the cyanides, the only 
poison with which prussic acid could well be clinically confounded is 
nitrobenzol. The distinction is often very difficult, large doses of 
the latter substance killing almost as quickly as prussic acid and 
inducing analogous symptoms. Caspar advises that after death the 
body be left open, exposed to the air, as the odor of prussic acid dis- 
appears rapidly, while that of nitrobenzol is persistent. The diseases 
with which the poisoning may be confounded most readily are some 
forms of apoplexie foudroyante, and sudden failure of the heart's 
action. The diagnosis may, during life, be almost impossible. It has 
been asserted that stertorous breathing does not occur in prussic 
acid poisoning; but it has been present in several reported cases.* 

* See Taylor's Medical Jurisprudence, Philadelphia, 1873, 363. 



CARDIAC DM PRESS A NTS 281 

An autopsy, however, ought generally to enable fche physician to 
determine whether the case has or has not been one of prussic acid 
poisoning, it' the symptoms during life are known. 

A curious rase of temporary hemiopia* apparently caused by the 
fumes of hydrocyanic acid, is reported. 

The period at which death may occur after the ingestion of the 
poison is sot down by Lonsdale at from one to fifty-five minutes; 
but a case has been observed by Hilton Fagge, in which the fatal 
result was put oft' for at least an hour and a quarter after the ingestion 
of hydrocyanic acid. After death the body often presents a livid 
surface, bloated countenance, fixed glassy eyes with dilated pupils, 
and clinched fingers; sometimes it offers nothing worthy of note 
except excessive rigidity, and the face may be very pale. When 
opened, the odor of prussic acid is generally, but not always, emitted; 
the mucous membrane of the stomach is very commonly found much 
congested, and the dark or cherry-colored liquid blood usually every- 
where fills up the veins. The heart is soft and flaccid. 

The treatment of poisoning by prussic acid is of little avail. Of 
the several chemical antidotes which have been proposed, hydrogen 
dioxide is the most practicable.! But such is the rapidity of absorption 
that the case is usually terminated before the antidote can be obtained. 
The asserted physiological antagonism of atropine has been disproved 
by Keen and by Boehm and Knie. The stomach should, if possible, 
be emptied or washed out with a thirty per cent, hydrogen-dioxide 
solution if at hand, and the hypodermic use of atropine and strych- 
nine as respiratory stimulants might be tried; the inhalation of the 
vapors of ammonia, and the free exhibition of ammonia by the mouth 
and by injection into the veins, may be practised. Artificial respira- 
tion has been found very successful by Preyer, and by Boehm and 
Knie, in animals, and should always be assiduously practised. Next 
to it in importance is the use of the alternate cold and hot douche, 
about a half of a small bucketful of cold water and the same quantity 
of very hot (115° F.) water being dashed upon the chest in rapid 
succession. There is considerable experimental evidence to show that 
the sodium hyposulphite is capable of following prussic acid, cyanides, 
nitrobenzol, and other nitrites into the system and there decompos- 
ing them, but we know of no case in which the antidote has been used 
upon man. As it is harmless it might be given hypodermically.| 

When potassium cyanide is taken into the stomach, the acids there 
present convert it into prussic acid, and the same change probably 
occurs, although more slowly, even when the salt is injected directly 
into the blood-vessels. The physiological, therapeutical, and toxi- 
cological properties of this salt are similar to those of prussic acid.§ 

* See B. M. J., 1884, i. 409. 

t See E. Merck, Merck's Arch., 1900, ii. 94. 

I See S. Lang, A. E, P. P., 1895, Bd. xxxvi.; J. F. Heymans and P. Masoin, A. I. P., 1897, 
iii. fasc. 1 and 2; R. Verbrugge, A. I. P., v. fasc. 3 and 4; and J. Meuriee, A. I. P., vii. fasc. 1 and 2. 

I Poisoning has occurred from the inhalation of the vapors of the cyanide and from absorption 
through the hands (Brit, and For. Med. Chir. Rev., July, 187G, 231). 



282 



GENERAL REMEDIES 



Death, however, does not occur so soon as from hydrocyanic acid, 
and insensibility is sometimes not manifested for several minutes. 
Five grains of the salt have caused death but fifty grains have been 
recovered from. (See McKelway.) 

Bitter Almonds (Amygdala Amard) yield a volatile oil, Oleum Amygdala 
Amarat, Oil of Bitter Almonds; of a yellowish color, bitter, acrid taste, with a 
strong odor of prussic acid. This volatile oil consists of not less than 85 per cent, 
benzoic aldehyde contaminated with various substances, of which the most impor- 
tant, prussic acid, is present in the proportion of from two to four per cent. Two 
drachms of the commercial oil are said to have caused death in ten minutes. Very 
properly, under the name of Benzaldehydum, U. S., Benzaldehyde, the pure benzoic 
aldehyde, produced synthetically or obtained from natural oils, has been recognized 
in the last edition of the U. S. Pharmacopoeia. This is a colorless, strongly 
refractive liquid, having a bitter odor and a burning taste. The official oil and 
benzaldehyde are very seldom used except as flavoring agents. 



REFERENCES. 



CARDIAC DEPRESSANTS. 



fothergill. 
Wood 



ackermann. . 

Brinton 

husemann. . . 

Masoin 

Mayerhofer. 



Mosso 

nobiling. . . . 
Radziejewski 
Richardson. . 
Salkowsky . . 

Sentz 

soloweitschyk 
Taylor 



..B. M. J., 1873. 
. .P. M. T., iii. 

ANTIMONY. 



.V. A. P. A., xxv. 531. 

.L. L., 1853, ii. 599. 

.Toxicologie, 853. 

.A. I. P., 1902, ii. 

. Nothnagel's Arzneimittel- 

lehre, Berlin, 1870, 219. 
.S. Jb., clxix. 236. 
.S. Jb., cxl. 24. 
.A. A. P., 1871. 
.L. L., 1856, i. 

.V. A. P. A., 1865, xxxiv. 78. 
. In. Dis., Dorpat, 1853. 
.A. E. P. P., xii. 440. 
.Guy H. R., Oct. 1857. 



VERATRUM VIRIDE. 

Blake Amer. Med. Weekly, 1874, 

No. 20. 

Eden A. E. P. P., 1892, xxix. 440. 

Wood P. M. T., iv. 

Wood, Jr U. P. M. B., 1908. 

ACONITE. 

Achschartjmow ..A. A. P., 1866. 

Bassot Thesis, Lyons, 1889. 

Boehm and Wartmann. Arbeit. Physiol. Wurz- 

burger Hochschule, 1873. 
Brunton and Cash. .St. Barthol. Hosp. Rep., 

1886, xxii. 
Cash and Dunstan. .Tr. R. S. London, 1898, 

cxc. 243. 

Ewers A. E. P. P., 1873, i. 

Guillaud A. de P., 1875. 

Harley St. Thomas Hosp. Rep., v. 

Labordk and Duquesnel. .Des Aconits, Paris, 

1883. 

Lewin Prager Vierteljahrs., cxxxi. 

Lhote and Vibert. .An. d'H., April. 
Liegeois and Hottot. .J. de P., 1861, 520. 
Mackenzie Pract., xx. 100. 



Matthews J. Ex. M., ii. No. 5. 

Nunneley Proc. Roy. Soc, London, 

1870. 

Plugge V. A. P. A. lxxxvii. 410. 

Reichert P. M. T., 1881, 105. 

Ringer and Murrell. .J. P., i. No. 4. 
Stevenson Guy H. R., 3 s., xxvi. 308. 

HYDROCYANIC ACID. 

Bischofp Ueber Vergift. nebst Ver- 

such. an Thieren, mit 
Blausiiure, etc., Wien, 
1844. 

Boehm and Knie.A. E. P. P., ii. 137. 

Bunge A. E. P. P., 1902, xii. 71. 

Coze Gazette M£d. de Paris, 1849. 

Fagge Guy H. R., 1868, 259. 

Fonke Sb. G. W., Leipzig, 1859, xi. 

28. 

Gaethgens Hoppe-Seyler's Med. Chem. 

Untersuch., Berlin, 1866. 

Hayashi and Muto. .A. E. P. P., 1902, xlviii. 

Hiller and Wagner. .L. L., 1877, ii. 933. 

Hoppe-Seyler .. .V. A. P. A., xxxviii. 475. 

Hunefeld Der Chemismus in d. thier- 

isch.Organis., LeiDzig,1840 

Jones N. Y. M. R., ii. 459". 

Keen Proc. Acad. Nat. Sci., Phila., 

1869. 

Kolliker V. A. P. A. x. 272. 

Laschkewitsch . . A. A. P., 1868, 652. 

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Rossbach and Papitzky. .C. M. W., 1877, 640. 

Schobarth Horn's Arch. f. Med. Erfalir- 

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cyanato, etc., Bonn, 1865. 
B. M. J., 1884, i. 409. 



ORDER III.— NUTRIANTS. 



FAMILY I.— ASTRINGENTS. 

Astringents arc those drugs which cause contraction of living 
tissues. That they do not act, as has been supposed, either by coagu- 
lating albumin or by calling into action the muscular function is 
demonstrated by the transitoriness of their effects, and by the fact 
that they influence tissues containing no muscular fibre. Every living 
soft tissue appears to possess a normal degree of condensation, which 
may be departed from on either hand: when this happens, in the 
one case the part is said to be relaxed, in the other to have its tonicity 
increased, or to be astringed. The action of astringents is always a 
local one, — i.e., produced not through the intervention of the nervous 
system, but by direct contact with the part affected. A pure astrin- 
gent should be capable of doing nothing beyond inducing contraction ; 
but in reality there is scarcely such a drug. Astringents are, when 
applied too freely, irritants. 

The concordant experimental results reached by M. Rosenstein 
and by R. Heinz show that medium solutions of tannic acid, alum, 
and the salts of lead, zinc, iron, copper, and mercury contract the 
blood-vessels by a direct action. When, however, the solutions are 
too strong, according to Heinz, this contraction is followed by dilata- 
tion. Both experimenters state that the silver nitrate is the most 
powerful in its influence, producing an almost permanent contraction. 
According to Rosenstein, acids cause dilatation of the capillaries. 

The clinical results obtained by the use of astringents in the treat- 
ment of inflammation can hardly be due to their action upon the 
blood-vessels, but seem to find more appropriate explanation in the 
-discovery of Heinz, that, locally applied, they decidedly check the 
out-wandering of the white blood-corpuscles, probably, as he thinks, 
by modifying the wall of the blood-vessel. 

The chief indication for the use of an astringent is the existence 
of relaxation. Local relaxation is commonly due to previous over- 
excitement. Thus, a throat is relaxed after over-use, or after 
inflammation. 

Astringents are more efficient as local than as general remedies, 
but in cases of inflammation care must be taken to use them in such 
a way that they shall not act as irritants. Applied too soon or too 
vigorously, they may do harm. These remarks are scarcely applicable 
to some of the mineral astringents, such as lead acetate or silver 
nitrate, which really appear to have sedative properties, and may 
with care be used advantageously in all stages of inflammation, when- 

283 



284 GENERAL REMEDIES 

ever there are distention and relaxation of the blood-vessels, although 
the general action of the part be that of nutritive excitement. 

Closely allied to relaxation is over-secretion, and astringents are 
constantly used to check morbid discharges. Indeed, these discharges 
are often simply the result of relaxation. Thus, Asp has experi- 
mentally proved that division of the intestinal nerves and consequent 
paralysis and relaxation of the vessels are followed by free watery 
secretion. In such cases the indication for astringents is very plain. 
But when a morbid discharge represents a high degree of inflammation, 
the same care must be practised in the use of astringents as in treating 
other local inflammations. Especially is this true since free secretion 
is often nature's method of relieving local inflammation. Thus, when 
abnormal alvine discharges are dependent upon intestinal relaxation, 
astringents are most valuable, but when they are dependent upon 
enteritis or colitis, astringents may do harm. 

If the morbid discharge by its profuseness endangers life, as in 
serous diarrhoea, astringents are urgently demanded. Very rarely, 
if ever, are these discharges other than paralytic in their origin; even, 
however, if they be due to over-action, an astringent may be necessary 
to check their excessiveness. 

Another indication for the use of astringents is to check hemor- 
rhage, and the same general reasoning is applicable to this as to the 
other indications. Hemorrhage dependent upon over-action demands 
other treatment than by astringents. Sometimes in these cases it is 
necessary, however, to check the hemorrhage at all hazards, and then 
astringents may be used in conjunction with other measures, although 
they may be to some extent contraindicated. Some of the astringents 
are employed locally to check hemorrhage due to traumatic or other 
ruptures of vessels. In such cases the astringents are employed as 
styptics, and do not act so much by their astringency as by coagulating 
the albumin of the blood and thus forming a clot and mechanically 
arresting the flow. 

Under certain circumstances there seems to be a general relaxation 
or loss of tone throughout the whole system, which may be best met 
by a consentaneous use of tonics and astringents. 

VEGETABLE ASTRINGENTS. 

The active principle of the vegetable astringents is tannic acid, 
and as it is almost their sole therapeutic principle and represents them 
very closely, it seems proper first to consider it, and afterwards to 
point out any especial therapeutic virtues the crude drugs of the 
class may possess. 

TANNIC ACID. 

There are two generic varieties of tannic acid, the gallo- and the 
kino-tannic: of these the former yields, upon exposure to the air in 
a moist state, gallic acid, the latter a gelatinous, inert substance. They 



ASTIUNtlKNTS 285 

are further distinguished by the color of the precipitates which 
they yield with the persalts of iron; gallo-tannic acid producing a 
blue-black, kino-tannic a green-black color. 

The official tannic acid — the gallo-tannic acid — is obtained by 
treating powdered galls with washed ether, which on standing sepa- 
rates into two strata, the upper of which is ethereal and contains chiefly 
the coloring-matter and other impurities. The lower watery stratum 
contains the tannic acid, which is recovered by evaporation. 

Commercial tannic acid is a light, feathery, non-crystalline powder, 
of a yellowish-white color, a faint odor, and an astringent, somewhat 
bitter taste. When absolutely pure, it is colorless and free from odor 
or taste other than that of astringency. Its reaction is strongly acid, 
and it unites freely with both organic and inorganic bases. It is very 
freely soluble in water, glycerin, and alcohol. With salts of the alka- 
loids it produces a whitish precipitate (tannates), very soluble in acetic 
acid; with persalts of iron, a black (bluish or greenish) precipitate. 

Official Preparations: 

Acidum Tannicum 10 to 20 grains (0.6-1.2 Gm.). 

Trochisci Acidi Tannici Each 1 grain (0.06 Gm.). 

Glyceritum Acidi Tannici (20 per cent.) Local use. 

Unguentum Acidi Tannici (20 per cent.) . . . .Local use. 
Collodium Stypticum (20 per cent.) Local use. 

Physiological Action.— Applied locally, tannic acid is a very 
powerful astringent, causing contraction, and in the case of a mucous 
membrane, great dryness. Sometimes, when it is used very freely, 
its irritant influence seems to overcome its astringent action, and we 
have seen diarrhoea result from its administration. Several experi- 
menters (Rosenstein, Fikentscher) have denied that it causes con- 
traction of the blood-vessels, because when they applied it to the 
exposed mesentery of a "Cohnheim frog," stasis of the blood, with 
dilatation of the vessels, not preceded by contraction, occurred. 
Daniels, however, using rabbits, obtained different results, and Lewin 
has shown that the method of experimentation was faulty. Clin- 
ical experience proves that tannic acid applied to relaxed mucous 
membranes affects their whole substance. 

Absorption and Elimination. — Although it was formerly believed 
that owing to the activity with which tannic acid coagulates albumin 
it was incapable of absorption, under certain circumstances a small 
amount of an alkaline tannate may be absorbed and circulate in the 
blood; but although a small portion of it may get into the blood as 
a tannate, what is absorbed is chiefly various decomposition products. 
Gallic acid has been found in the urine after the administration of 
tannic acid, but according to Morner the amount is less than one per 
cent, of the tannic acid ingested. When given in large amounts it 
mostly escapes absorption, and passes out with the feces unchanged. 

Thrown rapidly into the blood, tannic acid causes a fatal thrombosis; but 
Lewin asserts that when it is injected slowly and in moderate quantities the resulting 



2SG GENERAL REMEDIES 

albumin tannate is held in solution by the alkaline carbonates. He has also dis- 
covered that while tannin, in five-per-cent. solution, precipitates peptones out of 
watery solution, it is powerless in the presence of hydrochloric acid. Assuming 
the correctness of the investigations of Lewin, it is plain that tannic acid, when 
put in the stomach in small doses, must to some extent be absorbed unchanged. 
Lewin also asserts that it is, at least in part, eliminated unaltered, as he has fre- 
quently recovered it from the urine. At the same time it seems very probable that 
most of the tannic acid is converted into gallic acid, either in the stomach before 
absorption or subsequently in the system, since in the viscera of a rabbit poisoned 
with it, Schroff found only gallic acid; according to Claras, the greater part of 
ingested tannic acid can be recovered from the stools as albumin tannate or as 
gallic acid. The recent researches of Stockman afford a possible reconciliation of 
the results of Lewin with those of the older observers. Stockman finds that when 
tannic acid is given to the lower animals only a trace of it appears in the blood, 
while gallic acid can be obtained in abundance from the urine, with occasionally 
a small amount of tannic acid. If, however, sodium tannate be given, tannic acid 
appears in abundance in the urine, with a little gallic acid. The explanation offered 
by Stockman of this is probably correct, — namely, that tannic acid is usually con- 
verted in the stomach into an albuminous tannate, which is dissolved with great 
difficulty in the intestinal juices, so that time is afforded for the conversion of the 
tannic into gallic acid, whereas an alkaline tannate is absorbed at once and rapidly 
eliminated unchanged. 

Wohler and Frerichs have also found gallic acid with pyrogallic 
acid in the urine after the exhibition of tannic acid. 

After its conversion and absorption tannic acid still possesses 
astringent properties. Lewin has shown that in frogs poisoned with 
it the muscles are shortened and narrowed, and when loaded stretch 
less and recover their original length more nearly than do normal 
muscles. Kiichenmeister and Hennig state that in poisoned cats the 
spleen is notably diminished in size and increased in firmness; and 
Lewin has found in rabbits that tannic acid causes primary arrest of 
the urinaiy secretion, followed by a marked increase of the flow. 

Therapeutics. — As tannic acid undergoes in the system partial 
conversion into gallic acid, the latter is to be preferred to it when the 
part to be acted on can be reached only through the circulation. As 
a local application, tannic acid is much more powerful than gallic- 
acid. Locally applied it may be used to overcome relaxation, as in 
spongy gums, mercurial sore mouth, hemorrhoids, and chronic sore 
throat. To check hemorrhage it may be used whenever the source of 
the flow can be reached directty, as in epistaxis, hematemesis, hemor- 
rhage from the bowels, etc. To arrest excessive secretion it may be 
employed locally in leucorrhoea, diarrhoea, old abscesses, chronic ulcers, 
excessive perspiration, osmidrosis, and various diseases of the skin. 
It is also often very useful for the purpose of hardening parts exposed 
to friction, as in cases of sore nipples and tender feet. 

As an antidote it is useful in poisoning by various metals, especially 
antimony and iron. It is also a chemical antidote for the poisonous 
alkaloids; but, as the compounds it makes with them are slowly 
dissolved by the fluids of the alimentary canal, it must always be 
followed bv emetics and cathartics. 



ASTRINGENTS 287 

Administration. — When given (<> act on (lie stomach, as in licina- 
temesis, tannic acid should be in powder. When the bowel is to bo 
influenced, as in diarrhoea, the preparations of the various plants 
mentioned below are preferable as the colloid matterofthe cruder galen- 
icals protects the tannin from immediate precipitation in the stomach. 

Toxicology. — Tannic acid can scarcely be called poisonous; 
although Rollet reports the case of a young girl in whom a very large 
quantity of it induced severe gastric and abdominal pains, with 
obstinate vomiting and constipation, fever, and general malaise. 
Both Schroff and Judell assert that eighty grains of it cause no 
symptoms of importance in the rabbit. 

GALLIC ACID. 

Gallic acid is a white, powdery substance, in fine acicular prisms, 
soluble in S3 to 86 parts of water, in three parts of boiling water, 
and freely soluble in alcohol and in ether. Its taste is acidulous and 
astringent. 

According to the usual method, gallic acid is prepared by the 
exposure of moistened powdered nutgalls in a warm place for a month. 
A species of fermentation, with the development of a peculiar fungus, 
is said to occur, during which oxygen is absorbed, carbonic acid is 
evolved, and glucose and gallic acid are produced. M. Sacc has, 
however, denied this, affirming that the change is simply one of 
hydration, tannic acid being an anhydride of gallic acid. Tannic acid 
also may rapidly be converted into gallic acid by the action of dilute 
sulphuric acid. 

Gallic acid produces with persalts of iron a bluish precipitate, with 
lime-water a whitish precipitate, changing to blue and then to violet 
or purplish, — all of these precipitates being gallates. It does not 
coagulate gelatin or albumin, and is, therefore, not a styptic. As an 
astringent it is less powerful than tannic acid. It escapes from the 
body through the kidneys. 

Acidum Gallicum 15 to 30 grains (1-2 Gm.). 

Therapeutic Action. — Gallic acid is not nearly so efficient as 
tannic acid, when applied locally, but should always be preferred when 
the part is to be reached through the medium of the circulation. It 
is useful as an astringent in hemoptysis, hematuria, colliquative sweats, 
etc. It has been recommended in bronchoirhoea and in the profuse 
expectoration of chronic phthisis. In our hands, however, it has 
completely failed in the latter affections. In Bright's disease, when 
there is an abnormally large secretion of highly albuminous urine, it 
may lessen very materially the excretion of albumin. 

The following drugs which are recognized by the TJ. S. Pharmacopcea depend 
for their activity chiefly upon some form of tannic acid. 

Galls are produced on several varieties of oak trees by the wounds of various 
insects. The official nutgall is developed on the Quercus infectoria by the punc- 



288 GENERAL REMEDIES 

tures of the Cynips Tinctoria. There are two varieties of galls, derived chiefly from 
the Levant: the blue or green, which are the young galls gathered before the ova 
of the fly are hatched, and the white galls, which are light hollow bodies from which 
the young cynips has escaped. The latter contain but little tannic acid and the 
U. S. Pharmacopoeia, therefore, only recognizes the green variety. These are of a 
bluish olive green color, from the size of a pea to that of a hickory nut, externally 
smooth or more commonly marked with tubercles. They contain from fifty to 
eighty per cent, of gallotannic acid. 

Tinctura Gallae (20 per cent.) 1 fluidrachm (4 C.c). 

Unguentum Gallae (20 per cent.) External use. 

Gambir, also sometimes known as Pale Catechu, is an extract derived from 
Ourouparia Gambir. The extract occurs as irregular masses or cubes of a reddish 
or grayish-brown color with a bitter and very astringent and afterwards a sweetish 
taste. It contains from twenty-five to fifty per cent, of kinotannic acid. 

Tinctura Gambir Composita (5 per cent.). 2 fluidrachms (8 C.c). 

Trochisci Gambir Each contains 1 grain (0.06 Gm.). 

Kino is the dried juice of Pterocarpus Marsupium, an East Indian tree. It 
occurs in small irregular shining reddish fragments with a highly astringent taste, 
at first bitterish, but afterwards sweetish. It contains from sixty to seventy-five 
per cent, of kinotannic acid. 

Tinctura Kino (5 per cent.) 1 to 4 fluidrachms (4-15 C.c.). 

Hematoxylon is the heart wood of the Hematoxylon campechianum, or log- 
wood tree, a native of Central America. It is dense heavy wood of a deep reddish- 
brown color, containing besides kinotannic acid a crystalline principle hematoxylin, 
which, when pure, is yellow but readily yields red or purple dyes. 

According to Combemale, hematoxylin is capable of causing a fatal intoxica- 
tion, commencing with rigors and fever and ending in vomiting, anuria, coma and 
collapse. Its taste is sweetish., somewhat like that of licorice, and astringent. 

Extractum Haematoxyli 15 to 30 grains (1-2 Gm.). 

The following formula offers an efficient and elegant remedy for diarrhoeas 
of relaxation; the proportions may be varied to suit individual cases. R Ext. 
haematoxyli, 5 U > Acid, sulph. aromat., fohi; Tinct. opii camph., fgiss; Syrupi 
zingiberis, q. s. ad fgvi. M. — Dose, a tablespoonful, properly diluted. 

Rhus Glabra. — The U. S. Pharmacopoeia recognizes the berries of the sumac 
or Rhus glabra. They contain from six to twenty-five per cent, of tannin and are 
especially useful as a basis of mouth-washes or gargles on account of their pleasant 
taste. 

Fluidextractum Rhois Glabra? 15 minims (1 C.c). 

Locally it may be used in strengths of 15 to 30 per cent. 

Krameria, or rhatany, is the dried root of the Krameria triandra, Krameria 
ixina or Krameria argentea, South American shrubs. It contains from five to fifteen 
per cent, of a peculiar tannic acid. 

Extractum Krameria? 5 to 10 grains (0.3-0.6 Gm.). 

Fluidextractum Krameria? 10 to 20 minims (0.6-1.2 C.c). 

Syrupus Krameria? (45 per cent.) 20 to 30 minims (1.2-2 C.c). 

Tinctura Krameria? (20 per cent.) J to 1 fluidrachm (2-4 C.c). 

Trochisci Krameria? Each 1 grain (0.06 Gm.). 



ASTRINGENTS 289 

Oak. — The bark of many species of oak trees contains notable proportions of 
tannic acid. The U. S. Pharmacopiria recognizes only the bark of the Quercus 
alba or white oak. This contains from five to ten per cent, of quercitannic acid. 
It is used chiefly as a means of making cheap astringent infusions for external 
application. 

Fluidextractum Quercus 15 minims (1 C.c). 

Locally a 25 to 50 per cent, solution may be employed. 

Hamamelis, or witch-hazel, is an abundant native bush from which various 
preparations are made which enjoy extraordinary popularity for local applications. 
Their virtue depends chiefly upon the faith with which they are applied. The 
Pharmacopoeia recognizes both the bark and the leaves of the Hamamelis virginica. 

Aqua Hamamelidis External use. 

Fluidextractum Hamamelidis Foliorum J to 2 fluidrachms (2-8 C.c). 

Geranium is the rhizome of the Geranium maculatiun or cranesbill. It 
contains from ten to twenty-five per cent, of gallotannic acid. 

Fluidextractum Geranii ?, to 1 fluidrachm (2-4 C.c). 

Rose Leaves. — The dried petals of the Rosa gallica, or red rose, also contain 
a small percentage of tannin, but are used chiefly for their pleasant flavor. 

Fluidextractum Rosse J to 2 fluidrachms (2-8 C.c). 

Confectio Rosa? Excipient for pills. 

Mel Rosa; Vehicle. 

Syrupus Rosa? Vehicle. 

A number of unofficial compounds of tannic acid have come into 
vogue, some of them of great practical value. 

Tannalbin. Tannin albuminate. — This is a light-brown powder, insoluble in 
water or the gastric juice, but decomposed by the alkaline juices of the intestines 
with the liberation of its constituents. It is tasteless, odorless, and non-irritant. 
It is a very valuable remedy in the treatment of intestinal catarrh and relaxation 
requiring the use of an astringent, acting immediately, persistently, and effectively, 
and affording in many cases an excellent combination with bismuth subnitrate. It 
lias been recommended also in renal conditions associated with an excessive 
discharge of albumin. Dose, twenty to forty grains, in powder (1.2-2.5 Gm.). 

Tannacol. Gelatin tannate. — A tasteless, odorless powder, probably identical 
in its therapeutic application to tannalbin, although Rosenheim affirms that it is 
superior in that it is less apt to be affected by the gastric juice, and is of greater 
uniformity of constitution. Dose, fifteen to thirty grains (1-2 Gm.). 

Tannoplne. Tannon. — A combination of tannic acid and urotropin, which is 
said to contain eighty-seven per cent, of the acid, and, passing unchanged through 
the stomach, to undergo decomposition by the alkaline juice of the alimentary 
canal. It has been strongly recommended by Schreiber and other clinicians in the 
treatment of all forms of diarrh&as requiring an intestinal astringent. Dose, ten 
to fifteen grains (0.6-1 Gm.). 

Tannoform. — The tannojorms are combinations between tannins and formal- 
dehyde. Commercial tannoform is the condensation product of gallotannic acid 
and formaldehyde. It is a light, pinkish-white powder, which is believed to be 
decomposed by the alkaline juices of the intestines with the setting free of tannic 
acid and formaldehyde, and to act, therefore, as an astringent and antiseptic. It 
19 



290 GENERAL REMEDIES 

has been very highly recommended by numerous practitioners in tuberculous and 
other diarrhoeas requiring an astringent, both in adults and in children, given in 
doses of one-half to one grain (0.03-0.06 Gm.), in capsules, three times a day. 

There is also much testimony as to the value of tannoform as an external 
remedy. According to K. Ullmann, confirmed by F. Merz, tannoform is extremely 
efficient in hyperidrosis of the feet; a foot-bath should be used just at bedtime and 
a powder, composed of one part of tannoform and two parts of talc, should be well 
rubbed in between the toes and over the feet, daily for eight days. The effect is 
said to last many weeks. Tannoform has also been used as a local remedy in 
various external ulcerations, also eczemas, and other affections of the skin. 

ACETIC ACID. 

Absolute acetic acid, or as it is commonly called, glacial acetic 
acid, is at temperatures above 60° F. a clear colorless liquid with a 
strong pungent odor like that of vinegar and an intensely acid, caustic 
taste. At 59° F. it becomes a crystalline solid. It has a specific 
gravity of 1.049. The diluter solutions of acetic acid are liquids at 
all ordinary temperatures. Vinegar contains from five to ten per cent. 
of acetic acid and therefore corresponds approximately in strength 
with the official dilute acetic acid. 

Official Preparations: 

Acidum Aceticum Glaciale Not used internally. 

Acidum Aceticum (36 per cent.) Not used internally. 

Acidum Aceticum Dilutum (6 per cent.) \ to 1 fluidrachm (2-4 C.c). 

Local Action. — The strong solutions of acetic acid are intensely 
irritant, and the glacial acetic acid actively escharotic, — in a measure, 
no doubt, owing to its properties of dissolving gelatin and gelatinous 
tissue and of effecting a partial solution of albuminous matters. 

Dilute acetic acid or its equivalent, vinegar, acts upon the skin 
as a powerful stimulant and astringent, causing contraction of the 
vessels and great whiteness, so that it is often very useful as a topical 
application in various forms of dermatitis, especially sunburn, and 
also in bruises and sprains. We have found it, diluted with from one 
to four parts of water, a very grateful drink in hematemesis, and very 
effective in arresting the flow of blood. Diluted with two or three 
times its bulk of water, it is occasionally employed as an injection 
against seat-worms; but the infusion of quassia is preferable. 

The use of acetic acid as a caustic will be spoken of under the 
heading of Escharotics. 

Toxicology. — Acetic acid in any of its more concentrated forms is 
a corrosive poison, and death has been produced by it in at least one 
case (Orfila). The symptoms resemble those caused by mineral acids, 
and the treatment is exa jV similar, — neutralization by an alkali 
or its carbonate, or by some substance, such as soap, containing an 
alkali, and the meeting of indications as they arise. 

Agaric. — Under the name of Agaric various species of fungi belonging to the 
genus Boletus have been employed from time to time in medicine. Of these the 
white agaric, or purging agaric of writers, is obtained from Boletus laricis, the fungus 



ASTRINGENTS 291 

of the European larch. It contains a whitish, very bitter acid, variously known 
as agaric acid, or agaricinic m-itl, slightly soluble in cold water, moderately so in 
hot water. According to the researches of Hofmeister, agaric acid has upon the 
lower animals little influence except in arresting the secretion of sweat by paralyzing 
the peripheral nerves of the sweat-glands. Both the impure extract, known in 
commerce as agaricin, and agaric acid have been extensively used for the purpose 
of arresting colliquative sweats, and in our experience have proven valuable remedies. 
The oidy untoward effect ever produced, even by the largest dose, is irritation of 
the gastro-intestinal canal. Two to five grains (0.13-0.3 Gm.) of the agaricin may 
be given three times a day, commencing with the smaller dose and increasing. Ac- 
cording to Hofmeister, the dose of the pure acid is from one-fifteenth to one-third 
of a grain (0.004-0.02 Gm.). 

Cotarnine Hydrochlorate. Stypticin.— This salt, which is obtained by 
oxidizing narcotine, occurs in yellow crystals, readily soluble in water and alcohol. 
Falk found that cotarnine caused in frogs paralysis by depression of the motor 
side of the spinal cord, and in warm-blooded animals acts as a depressant both 
upon the cerebral cortex and motor cord, causing narcosis with paralysis. He 
further determined that it has no direct influence upon the circulation; and that 
upon the respiration it acts as a primary stimulant and secondary depressant, 
causing death by central asphyxia when given in toxic dose. Abundant clinical 
evidence has been published to show that cotarnine is a valuable remedy, as first 
stated by Freund, in Menorrhagia as well as in pulmonic and other internal hemor- 
rhages. It is said, also, to be a powerful local hemostatic. Cotarnine gauze, or 
absorbent cotton saturated with cotarnine, has been greatly praised by dentists 
and surgeons. 

As Mohr in his experiments with the drug failed to produce uterine contrac- 
tions it seems probable that cotarnine arrests hemorrhage by some sort of astringent 
action, or by directly affecting the blood; but further physiological investigation is 
imperative for decision. In excessive menstruation half a grain may be given three 
or four times a day for four days before the expected discharge; the dose being 
increased to one grain when menstruation appears. In hemoptysis three grains 
may be administered at once subcutaneously, and repeated in half an hour if required. 

MINERAL ASTRINGENTS. 
ALUMINUM. 

The salts of aluminum are all possessed of more or less active 
astringent properties. The one most frequently used and also one 
of the most powerful is the double sulphate of aluminum and 
potassium or alum. 

Owing to the cheapness of ammonia the double salt of alumina 
and ammonium has been largely substituted for the true alum, which 
contains potash and is alone recognized by the U. S. Pharmacopoeia. 
The physical qualities of the two salts are identical, but the ammonia 
alum, when triturated with lime, betrays its nature by the evolved 
gas. Alum occurs in octahedral colorless crystals, which are often 
aggregated into large masses. Its tas^e is astringent, acidulous, and 
sweetish. It is soluble in nine parts uf water at 59° F. and in one- 
third part of boiling water. It is slightly efflorescent, and when heated 
parts with its water of crystallization and is converted into a white 
powder (Dried Alum). The alkalies and their carbonates, lime, mag- 
nesia, and its carbonate, potassium tartrate, and lead acetate are 
incompatible with alum. 



292 GENERAL REMEDIES 

Aluminum sulphate usually occurs in flattened crystalline cakes, 
of a sour-sweetish, somewhat astringent taste and acid reaction. It 
is soluble in twice its weight in water. It is an irritant active astrin- 
gent, with some germicidal power. Its solution, in strength varying 
from half an ounce to the pint up to saturation, has been used as a 
local application for foul ulcers, leucorrhoea, and other allied diseases. 
In solid form, or even in saturated solution, it is very feebly caustic. 

Aluminum hydroxide is a white, amorphous, odorless, tasteless, per- 
manent powder, insoluble in water and alcohol, which has been used as 
a feebly astringent, desiccant powder in inflammatory skin conditions. 

Official Preparations: 

Alumini Hydroxidum External use. 

Alumini Sulphas External use. 

Alumen (Alum) 10 to 20 grains (0.6-1.2 Gm.). 

Alumen Exsiccatum (Dried Alum) External use. 

Physiological Action. — According to the statements of G. B. 
Wood and A. Stille, aluminum can be detected in the urine of persons 
to whom alum has been given, so that it or its derivatives must find 
a way into the blood. In dilute solution it is a powerful astringent; in 
concentrated form, irritant; as dried alum, mildly corrosive. In 
large dose in the lower animals it produces violent gastro-intestinal 
irritation, and is capable in man of causing death, preceded by vio- 
lent vomiting, bloody purging, and hematuria (Kramolik). One ounce 
and five drachms of burnt alum caused death in eight hours. 

Therapeutics. — Internally alum is of no value in practical medi- 
cine, except it be in colica pictonum, in which it is asserted by authority 
that it is a valuable remedy even though there be no lead in the 
primal vice to be precipitated by it as a sulphate. As a local drug it 
is of especial value as a styptic by virtue of its powerful coagulative 
influence on albumin; and we have known it usefully given by atomi- 
zation in hemoptysis. It is sometimes used in various anginas and 
other inflamed conditions of the mucous membrane, but is so irritant 
and attacks so strongly the teeth as to greatly lessen its value. 

In colliquative sweats, sponging at bedtime with alum-water, or, 
still better, the taking of an alum-water bath, will often materially 
aid in restoring the lost tone to the skin. In chronic ulcers with 
exuberant spongy granulations, and in certain conditions of con- 
junctivitis, alum curd is often applied with benefit. When it is desired 
to exert an astringent action upon the internal organs, alum is not 
useful. As a mechanical emetic it is too uncertain to be of much value. 
Alum curd ma}' be made by dissolving two drachms in a pint of milk 
and straining, or by rubbing the alum with white of egg. Dried alum 
is sometimes used as a very mild escharotic for the destruction of 
exuberant granulations in ulcers. 

Aluminum hydroxide is much less irritant than alum and also 
less actively astringent. It is useful in the form of an ointment in 
minor burns and various irritations of the skin. . 



ASTRINGENTS 293 

LEAD. 

There are five salts of lead, exclusive of the plasters, which are 
recognized by the Pharmacopoeia. 

Lead acetate or Sugar of had occurs in transparent, acicular, often 
aggregated, crystals, of a sweet, styptic taste. It is soluble in water, 
to which it usually imparts a slight milkiness. From its solution it 
is precipitated black by sulphuretted hydrogen, white by soluble 
carbonates, chlorides, and sulphates, and bright yellow by potassium 
iodide. It is also incompatible with the mucilage of slippery elm, 
but scarcely so with that of flaxseed or of pith of sassafras. 

The solution of lead subacetate, sometimes known as Goulard's 
Extract, is made by boiling lead acetate and lead oxide together. 
It contains twenty-five per cent, of lead subacetate. The approxi- 
mate formula is Pb 2 0(CH :j COO).,. The liquor plumbi subacetatis 
dilutum contains but one per cent, of lead subacetate and is too feeble 
for any use. Neither of these preparations is used except externally. 

Lead nitrate occurs in white, nearly opaque, octahedral, very heavy 
crystals, soluble in two parts of water at 59° F., and in 0.75 part of boil- 
ing water; almost insoluble in alcohol. Used chiefly as a disinfectant. 

Lead oxide or Litharge, which is prepared by blowing air through 
melted lead, occurs in small yellowish or orange-colored scales, which 
are insoluble in water and alcohol, but are soluble in acetic or dilute 
nitric acid and in a warm solution of the fixed alkalies. It is occasion- 
ally used as a desiccant astringent powder for ulcers, but its chief 
employment in medicine is in the making of T^ead Plaster, which 
consists chiefly of lead oleomargarate. Lead plaster occurs in grayish, 
cylindrical rolls, which become adhesive at the temperature of the 
body, and, spread upon kid, is sometimes used as a protective to 
parts exposed to pressure, or to superficial ulcers or abrasions. 

Soap Plaster is made by the addition of soap to lead plaster. It 
is employed chiefly as a protective. 

Lead carbonate is a heavy, white, tasteless powder, insoluble in 
distilled water but slightly soluble in water containing carbonic acid. 
Rubbed up with linseed oil it constitutes white lead paint. An 
ointment containing ten per cent, was formerly official. 

Lead iodide is a heavy yellow powder, insoluble in water, without 
odor and taste. It has probably no therapeutic virtues, though 
occasionally used as a local application to ulcers. 

Official Preparations: 

Plumbi Acetas 1 to 3 grains (0.06-0.2 Gm.). 

Plumbi Iodidum Not used internally. 

Plumbi Oxidum Not used internally. 

Liquor Plumbi Subacetatis [Lead Water; 

Goulard's Extract] External use. 

Liquor Plumbi Subacetatis Dilutum External use.' 

Emplastrum Plumbi External use. 

Emplastrum Saponis External use. 

Ceratum Plumbi Subacetatis External use. 



294 GENERAL REMEDIES 

When a soluble salt of lead is applied to a part in not too concen- 
trated solution, it acts as an astringent and sedative. Owing to the 
contraction of the vessels which is induced, the tissue becomes blanched 
and any inflammatory action which may be present is remarkably 
affected. When in concentrated solution, the mildest preparations 
of lead are capable of acting as irritants, increasing or even originating 
inflammation. When the salts of lead are taken internally in thera- 
peutic doses, no decided symptoms are generally induced, except a 
diminution of the secretions, especially of those of the alimentary 
canal. Sometimes, when full therapeutic doses are exhibited, a slight 
lowering of the frequency and force of the pulse is said to result, but 
we have never witnessed this. The insoluble are much less irritant 
than the soluble lead preparations. 

Therapeutics. — The salts of lead are used for their astringent action 
and also as mechanical protectives. The insoluble salts are much less 
actively astringent than the soluble salts. Of the latter, for internal 
administration, preference is given to the acetate; although com- 
mended by G. B. Wood in the treatment of hemoptysis, practically 
the only condition in which it is at present employed is in the treat- 
ment of diarrhoea. On account of its sedative properties, when the 
purging is attended by inflammation it is one of the most serviceable 
of all the astringents, and owing to the promptness of its action it is 
also very valuable in cases with profuse serous discharges. It is given 
in pill form, frequently combined with opium. 

The solution of lead subacetate, commonly known as "lead water," 
is a very popular external application in cases of sprains and bruises 
as well as in superficial inflammation. For this purpose it should be 
diluted with from four to ten times its bulk of water or alcohol. The 
official diluted solution is too weak to be of value. 

Lead nitrate forms the base of Ledoyen's disinfectant solution. 
It acts by decomposing the sulphuretted hydrogen, itself being con- 
verted into a lead sulphide. Lead nitrate is frequently used in the 
treatment of onychia maligna; the dead part of the nail should be cut 
away and the powdered nitrate thickly sprinkled over the surface; after 
a few days the slough separates, leaving a skin surface upon which the 
new nail soon forms. Sometimes more than one application is required. 

The insoluble lead carbonate is used to some extent as a sedative 
protective application, especially in the treatment of burns. For this 
purpose an ointment may be employed. Care must be taken in its 
use, however, when a large surface is involved, as lead colic has been 
caused by its absorption. 

Lead plaster is sometimes used as a protective to parts exposed to 
pressure. It also enters into the composition of adhesive and soap 
plasters, which are used chiefly for mechanical purposes. 

Toxicology. — Acute lead-poisoning is usually produced by a 
soluble salt, notably the acetate;* but a case reported by Freyer 

* According to Husemann (Handbuch der Toxicologie), the poudre de succession, so famous 
during the reign of Louis XIV., was composed chiefly of lead acetate. 



ASTRINGENTS 295 

shows that white load and other insoluble preparations may act as 
violent and even fatal irritant poisons. When the acetate is ingested 
in toxic dose, the first symptom is usually a persistent, sweet, some- 
what metallic taste; this in a few minutes is followed by vomiting, 
which may or may not be preceded by nausea. The matters vomited 
are often milky white, from the presence of lead chloride. A severe 
burning persistent pain in the abdomen now comes on, and is accom- 
panied by a craving for drink. There may be obstinate constipation, 
or diarrhoea may ensue: in either case the stools are generally black 
from the sulphuret of lead. In certain cases a state of collapse is 
developed; the pulse falls to forty or fifty per minute, the voice is 
lost, the face is deadly pale, the lips are livid, and syncope seems 
imminent. In other instances the nervous symptoms may predomi- 
nate, or they may accompany those of disordered circulation: cramps 
in the calves of the legs, severe neuralgic pains in the extremities, 
paralysis and anesthesia, vertigo, stupor, may any or all of them be 
present. In fatal cases, coma, with or without convulsions, finally 
develops. A distinctive mark of lead-poisoning, which occasionally 
is present very early, is the blue line upon the gums. After death 
inflammation of the alimentary mucous membrane is sometimes, 
but not always, found. One ounce of lead acetate, subacetate, or 
nitrate may take life. 

The treatment of acute lead-poisoning consists in the evacuation of 
the stomach, the exhibition of sodium or magnesium sulphate, and 
the meeting of the indications as they arise. The Epsom and Glauber's 
salts act as chemical antidotes, by precipitating the insoluble sulphate 
of lead, and also, if in excess, empty the bowel of the compound 
formed. To allay the gastro-intestinal irritation, albuminous drinks 
should be given and opium freely exhibited. 

Chronic Lead-poisoning. — Chronic lead-poisoning, or saturnism, is 
almost always accidental, and occurs most frequently among those 
wdiose occupation exposes them to daily contact with some compound 
of the metal; manufacturers of white lead, painters, glaziers, and 
similar artisans furnish the greater number of victims. It may be 
seen, however, in persons of all conditions of life, for although neither 
food nor drink is often purposely adulterated with lead, yet it is 
frequently introduced into the system accidentally along with those 
necessities. Lead pipes are habitually used for the conveyance of 
water, and when the water contains salts of lime, even in minute 
proportion, no evil results, because through the decomposition which 
ensues insoluble coatings are deposited on the inside of the pipes.* 
When the water is pure, no such reactions occurring, the lead is slowly 
dissolved in the form of a carbonate, and poisoning may result. Poi- 
soning has also frequently resulted from the employment of cosmetics 
and hair-dyes, from the internal or external medical use of lead prepa- 
rations, from cooking bread with painted wood, from imperfectly 

* For an elaborate article on the chemical relation of water to lead, see Schmidt's Jahrbiicher, 
cxliv. 279. 



296 GENERAL REMEDIES 

burnt pottery, from habitually biting silk thread which rascally 
manufacturers often load with lead to give weight to it,* from lead 
bullets retained in the body (Vucetio), and from diachylon used as 
an abortifacient (Ransom), etc. 

Two types of saturnism are recognized. The first in which colic 
is the most decided symptom is often spoken of as subacute. After 
some days of malaise and wretchedness, or sometimes very suddenly, 
the victim is taken with abdominal colicky pains, which increase in 
intensity until they become very severe. They are constant, with 
occasional exacerbations, are sometimes dull, sometimes sharp, are 
generally described as twisting, and seem to centre around the umbili- 
cus. Very often there are repeated retching and vomiting. The walls 
of the abdomen are retracted, rigid, knotted; the bowels are obsti- 
nately costive; the tongue is contracted and whitish, the appetite 
gone, and the thirst sometimes excessive. Neuralgic pains in the tho- 
rax and in the extremities are of frequent occurrence. In some cases 
the conjunctiva is distinctly icteroid. This condition, which is known 
as colica pictonum, or lead colic, may after a time abate, and the patient 
convalesce; more usually, however, the attacks recur from time to 
time, becoming gradually less severe and distinctive, and the patient 
gradually passes into chronic lead-poisoning. Occasionally the colic 
increases in severity; sometimes the course of the disease is 
interrupted by various violent accidents. 

In the second form of chronic lead-poisoning the abdominal 
symptoms may or may not be present, but the most marked features 
are referred to other organs, more commonly to the nervous system. 
The manifestations of lead intoxication, may, however, vary so much in 
their symptomatology as almost to baffle concise description. It has 
seemed to us that the symptoms can best be studied by arranging 
the cases in groups, but it must be remembered that in nature not 
only do these groups shade into one another, but also that there are 
all kinds of mixed cases, — cases which offer simultaneously or 
successively symptoms of two or more of these various groups. 

The first group contains the great bulk of cases of chronic lead- 
poisoning, at least as seen in this country. The symptoms consist 
of failure of health, more or less digestive disturbance, and double 
wrist-drop, — i.e., paralysis of the extensor muscles of each hand. 
Not rarely, the only noticeable symptom is the wrist-drop, the general 
health seeming to be very good. The true nature of such cases can 
usually be at once recognized by the bilateral character of the wrist- 
drop, cerebral and pressure paralyses being almost invariably unilate- 
ral. We have seen, however, bilateral pressure palsy, and also one 
or two cases of unilateral plumbic wrist-drop, due to a local absorption 
of lead, in artisans who had one hand much of the time in a prepara- 
tion of the metal. Similar cases have been recorded by Manouvriez.f 

* Chronic lead-poisoning is produced much, more frequently by insoluble than by soluble 
compounds of lead, but it is probable that any saturnine preparation may cause it. Thus, lead 
chromaie has killed numbers of people. (See Med. News, ii. 1887; also Therap. Gaz., iv.) 

t See also La France Med., 1882, i. 829. 



ASTRINGENTS 297 

The wrist-drop may exist alone, but not rarely there is with it anes- 
thesia of the affected part, or sometimes of the shoulders or other 
unparalyzed portion of the body. When the paralysis is complete, the 
electro-contractility of the muscles is in great, part or altogether absent. 
The rarer forms of chronic lead-poisoning may be divided into the 
cerebral, the periphero-spinal, and the nutritive. In the cerebral 
cases should be included those which are commonly spoken of as 
encephalopathies saturnina, or saturnine cerebritis.* 

In cerebral cases of lead-poisoning the violent brain symptoms may develop 
with great suddenness, or may be preceded by some days of headache, giddiness, 
sleeplessness, disturbed vision, strabismus, tinnitus auriuin, psychical aberration, or 
other prodromes of brain disturbance. Delirium, which is among the chief mani- 
festations of the fully formed condition, may be mild, but is often maniacal; stupor 
may replace or alternate with it; and violent epileptiform convulsions, ending in 
coma, are not infrequent. These convulsions are usually the precursors of death, 
but recovery may occur even after the most severe symptoms. 

Without the development of such severe symptoms, headache, loss of memory, 
giddiness, somnolence, hemianesthesia, disturbance of the special senses, aphasia, 
monoplegia, hemiplegia, or multiple cerebral palsies may occur during chronic 
lead-poisoning. Death, preceded by severe cerebral symptoms, may take place 
without organic lesion; but usually, when focal symptoms have been present, 
localized alteration of brain structure, secondary to diseases of the cerebral vessels, 
or to clu-onic inflammation of the brain or its membranes, can be detected. Some- 
times the cerebral symptoms are uremic; indeed, true plumbic encephalopathy 
and plumbic uremia from contracted kidney may coexist. Again, the more serious 
affection may be masked by a saturnine hysteria, since cases have been reported by 
Charcot and by Dutil in which hysterical hemianesthesia, amaurosis, anosmia, loss 
of sense of taste, and other cerebral symptoms have been the outcome of a major 
hysteria due to chronic lead-poisoning. Such cases as these probably occur only 
in individuals of previously hysterical temperament, and must be extremely rare in 
persons not of the so-called Latin race. 

Disturbances of vision are so frequent and so marked in lead-poisoning as to 
deserve special mention. They have been classified by De Schweinitz as follows: 

1. Transient amblyopia, without ophthalmoscopic change. 

2. Amblyopia without fundus lesions, or with congestion of the nerve-head, 
and with central scotomas analogous to those caused by other toxic agents. 

3. Optic neuritis, or neuro-retinitis, either specifically due to lead or secondary 
to changes in the brain or kidneys. 

4. Optic nerve atrophy, either consecutive to a plumbic papillitis or retrobulbar 
neuritis, or due to a primary effect of the lead on the visual organ. 

5. Various types of retinitis, vasculitis, and perivasculitis, either primarily due 
to lead or secondary to nephritis. 

Strabismus from muscular paralysis is sometimes of saturnine origin. f 

The second group of cases of chronic lead-poisoning consists of those 
in which the nerve-symptoms apparently originate below the cerebrum. 

In the present group belong cases such as have been reported by Putnam, by 
Tisier, by Raymond, and by G. L. Walton, in which the phenomena resemble those 
of locomotor ataxia, except in the presence of tenderness over the nerve-trunks, 

* George F. Crooke reports a case in which lead plaster taken for the production of abortion 
caused not only miscarriage, but also fatal brain lesions, preceded by choked disks, albuminuria, 
and convulsions. 

t For discussion of details, see Manouvriez (Arch, de Physiol. Norm, el Palholog., 1870, 411, 
1870, 702), A. De Cours {De V Hemianesthesia saturnine, Paris, 1875), Proust (Progris Mid., 1879; 
TO. j4fi), and Alex. Westphal (Archiv [iir Psychiat., 1887-88, xix.). 



298 GENERAL REMEDIES 

preservation of the tendon reflexes, or some other atypical symptoms. We have 
seen several cases in which the symptoms resembled those of an acute poliomyelitis, 
consisting chiefly of wide-spread paralyses with rapid wasting of the muscles. These 
cases usually can be differentiated by the presence of violent neuralgic pains, 
paralysis of the bladder and rectum, or other atypical symptoms. Similar to these 
cases are those spoken of by G. Lyon, in which a rapid general paralysis spread from 
part to part, until at last aphonia and dyspnoea, and even death from asphyxia, 
resulted. Severe intractable chorea lias been produced by lead. Oscar Buber 
calls attention to the form of irregular lead palsy in which the paralyzed muscles 
are affected with peculiar slow, worm-like, and occasionally painful contractions. 
Disturbances of sensation may occur in lead-poisoning; anesthesias are, perhaps, 
not very rare, and violent neuralgic pains, probably due to neuritis, may be the 
chief manifestation. In a case of H. C. Wood's in which the diagnosis was confirmed 
by finding lead in the drinking-water and in the urine of the patient, the symptoms 
were intense general pruritus, with violent neuralgic pains shooting through the 
rectum and the urethra, coming on at night and producing an insomnia which 
appeared to be unconquerable. The lesion is often peripheral, and the very rapid 
pulse seen in some cases may be due to disease of the vagi, which Prevost and Binet 
have found degenerated. 

The third group of cases comprises those in which the poison 
chiefly expends itself upon glandular or visceral organs, or in 
producing wide-spread nutritive changes. 

It would seem that almost any of the vital structures may undergo degenera- 
tion. Potain reports a case of saturnine cirrhosis of the liver; while Valence and 
Claisse and Dupre call attention to plumbic parotiditis, which may take the form 
of a slowly progressive chronic hypertrophy of the gland, with dryness of the mouth, 
or of a distinct sclerosis, or there may be ulceration of the orifice of Steno's duct 
and obstruction. Rudolf Maier has found in poisoned animals atrophic degenera- 
tions of the intestinal glands and walls. Sailor found in twelve cases of saturnism 
a constant reduction in the secretion of hydrochloric acid. 

Of great frequency and importance are the lesions produced by lead in the 
kidneys. It must be remembered that temporary albuminuria may occur in lead- 
poisoning without serious implication of the kidneys; while, on the other hand, 
fatal nephritis may exist when there is no albumin in the urine (Lancereaux). A 
persistent low specific gravity of the urine in lead-poisoning is a symptom of the 
utmost gravity. Geppert confirms the observation, previously made by Olivier, 
that in temporary plumbic albuminuria many isolated kidney epithelial cells may 
often be found in the urinary sediments; and it is evident that a persistence of this 
condition must end in chronic renal disease. After death, which may be induced 
by uremia, the kidneys are found contracted, granular, with excessive development 
of the fibrous tissue (followed by contraction) and great thickening of the walls of 
the blood-vessels; these changes are identical with those of contracted kidney 
produced by gouty and other irritant poisons. As Ellenberger and Hofmeister have 
shown that the lead is chiefly eliminated by the kidneys, the frequency of plumbic 
nephritis is easily explained; but it is not readily perceived why it is so frequently 
associated with an arthralgia whose course and lesions closely simulate those of 
chronic gout. Garrod (1859), Dickinson, Lancereaux, Rosenstein, Leyden, and 
other authors have reported so many cases of this association of renal and gouty 
manifestations that it Can scarcely be doubted that the plumbism is the cause of the 
gouty symptoms, and not simply a complication of gout.* 

There are certain cases of lead-poisoning which do not conform 
to any of the types as yet given. 

* Consult Deutsch. Med. Wochenschrift, 1883, 185, 351; 1884, 129; also Paul Musehold (Die 
Bleivergijtung, Berlin, 1883). We have ourselves seen one case. 



ASTRINGENTS 299 

Among those very irregular cases may be mentioned those reported by E. 
Levy, in which acute asthma was produced by the inhalation of the dust, of white 
lead. Again, chronic saturnine asthma is sometimes seen in feoUe, narrow- -chested 
people, .lames J, Putnam calls attention to the fact that in lead-poisoning of chil- 
dren the legs and fool are commonly paralyzed. I'agliano has reported a case 

of saturnine facial palsy. It has been abundantly proved both by clinical experience 

and by experiments made upon the lower animals that, in chronic lead-poisoning 
the metal may pass through the placenta into the hot us, causing its death, with 
subsequent abort ion.* 

As any of the obscure manifestations of lead-poisoning may oxist, 
and even prove fatal, without a distinct history of other more char- 
acteristic phenomena, great care is sometimes necessary to avoid 
being misled, and not rarely the true nature of saturnine epilepsy or 
of saturnine albuminuria is overlooked. Hence the importance of the 
blue line upon the gums where they join the teeth, which is very common 
in persons suffering from lead-poisoning. It is said to be the result 
of a formation of lead sulphide in the walls of the capillaries. As was 
first pointed out by J. J. Putnam, chronic lead-poisoning may exist 
without this blue line upon the gums. Under such circumstances, 
if the symptoms be obscure the diagnosis can be established only 
through a chemical examination of the urine. f The practitioner 
should see that the urine which is to be sent to the chemist for examina- 
tion be slightly acidified, that directly after passing it be put in flint- 
glass bottles, and that it be at least a quart in quantity. From a 
diagnostic point of view an extremely important observation, if it 
be confirmed, is that of Deroide and Lecompt, who assert that there 
is in the urine of saturnine patients urohematoporphyrine, a red 
pigment, soluble in ether, water, and alcohol, which can readily be 
recognized by the spectroscope. 

In those cases of lead-poisoning which pursue a slow course to 
death the paralysis involves after a time the extensors of the lower 
as well as of the upper extremities, epileptic paroxysms occur at 
intervals, racking pains shoot through the limbs, points of cutaneous 
anesthesia appear, and often albuminuria aids in producing the fatal 
issue. Gradually the patient becomes more and more cachectic, 
general oedema and the whitened skin betray the increasing anemia, 
the paralysis extends from muscle to muscle, locomotion becomes 
impossible, and, if a convulsion or other accident do not close 
the scene, death at last takes place from loss of power in the 
respiratory muscles. 

Plumbic anemia is probably due, at least in part, to a direct action of the lead 
upon the blood or the blood-making organs. According to Malassez, the red blood- 
corpuscles during the anemias are not only diminished in number, but also increased 
in size. Sabrazes and Bourret have found in the blood of a case of serious acute 
lead-poisoning normoblasts, basophilic, granular, and polychromatic cells, also 

* See Constantine Paul (Archiv Gen., 1800, xv.), Legrand and Winter (Compt.-Revd. Soc. 
Biolog., 1889), and B. Annino (Schmidt's Jahrb., ccxliv., No. 11). 

t For an elaborate discussion, see leading article in Therap. Gaz., Dec. 1887; Ibid., iii. 813, 
and iv 92. 



300 GENERAL REMEDIES 

neutrophilic, polymorphonuclear leucocytes. In chronic lead-poisoning, Moritz 
found granulation of the basophilic erythrocytes, and was able to produce 
such a change in lower animals. 

After death lead has frequently been detected in almost all of the 
tissues. 

Heubel found most of it in the bones, and less in the muscular than in the 
nervous system. Chatin obtained from the cervical spinal cord three in one hun- 
dred and fifty parts. In the studies of Ellenberger and V. Hofmeister the liver 
and kidneys were found to contain the most lead, after them the bones, then 
the nerve-centres, and finally the flesh. Prevost and Binet found the lead 
in all the tissues, but believe that it especially accumulates in the kidneys.* 
G. N. Pitt reports finding over forty-seven grains of the lead sulphide in nine 
inches of the colon. 

The electro-muscular contractility is affected very early in lead- 
poisoning, and may be lost before the voluntary movements. It is 
stated by M. Raymond that the short extensor of the thumb preserves 
its function when all the other extensor muscles are paralyzed. The 
paralyzed muscles are finally exceedingly wasted, and their structure 
may be so totally destroyed that scarcely a single striated fibre can 
be found. The nerve-trunks are lessened in size, in many of their 
tubules the medulla has been replaced by fatty granules, and in some 
cases every trace of the tubules has disappeared and the nerve has 
been reduced to a fibrous cord. 

According to the researches of Degerine, the first appearance of change in a 
nerve-trunk consists in the myeline becoming broken up into blocks, and the nature 
of the change is a commingling of a parenchymatous and an interstitial neuritis, 
which both Degerine and Vulpian have traced upward as far as the anterior spinal 
roots. Lancereaux, Westphal, Friedlander, and others may be cited as having 
found very distinct peripheral lesions in lead-poisoning. Whether these lesions 
begin in the nerve or in the muscles cannot be considered as determined. Birdsall 
reported a case of what he believed to be a plumbic myositis, and Gourbault de- 
scribes primary alteration in the nerves, similar to those seen after section, as occur- 
ring in poisoned guinea-pigs, while Debove and Reaut describe the first changes as 
resembling those of subacute myositis, and Friedlander emphatically asserts that- 
lessening in the size of the muscular fibres and multiplication of the muscular nuclei 

* A question of the most serious importance, which at present we are not able to answer 
positively, is as to whether sclerosis, neuritis, and other chronic affections of the nervous system 
which have been reckoned as idiopathic or of unknown origin are not frequently the outcome of an 
entirely latent lead-poisoning. In a remarkable paper, J. J. Putnam, of Boston (.Trans. Assoc. 
American Physicians, ii.), describes cases entirely apart from recognized types of lead-poisoning, 
in which the metal was found in the urine. These cases may be grouped as follows: 1. Trembling 
of hands; sense of coldness and numbness in toes; lancinating pains in legs; fatigue on exertion. 
2. Marked progressive spastic paraplegia, with myosis and pupillary reactions; ataxia and some 
atrophy of hands. 3. Progressive weakness and stiffness in legs, with diffused and almost universal 
pains; marked tremor. 4. Temporary pain in chest, with slight dyspnoea; progressive numbness, 
heaviness, and weakness in legs. 5. Numbness in feet and legs, with impairment of strength; 
tremor of hands and tongue; some wasting of small muscles of hands; temporary retention of 
urine. Closely connected with this subject is the question whether lead may not be for a length of 
time in the system and appear in the urine without doing injury to the health. In a paper (Boston 
Med. and. Surg. Journ., 1890, cxxiii.) Putnam brings forward more facts, whose import is at present 
very doubtful. In an examination of the urine of sixty-eight persons, presenting no evidences of 
any disarrangement of health, lead was found in the proportion of about seventeen per cent., while 
the urine of thirty-six persons suffering from chronic and subchronic affection of the nerves, nerve- 
centres, and spinal cord contained lead in the proportion of fifty per cent. In the last group were 
cases of tremors with debility, of chronic multiple neuritis, multiple sclerosis, spastic paraplegia, 
muscular atrophy, epilepsy, sciatica, digestive disorders, etc. (Bosl. Med. and Surg. Journ., 1889, 
cxxi.). One cannot help suspecting that, owing to defective water-supply, Bostonians are especially 
prone to contain lead. For a minute description of various forms of lead palsy, see Le Saturnisme, 
Meillere, Paris, 1903. 



ASTRINGENTS 301 

precede the nerve-degeneration. On the other hand, Yulpian, Monakow, Oellcr, 
and a nuniher of other observers* have noticed structural changes (poliomyelitis, 
capillary hemorrhages, etc.) in the spinal cord of men dead of plumhism; while 
Popow found thai when guinea-pigs were rapidly poisoned (six to eight days) with 
lead there was produced a central myelitis, which first affected the large fells of the 
gray matter, and afterwards involved the white matter, the peripheral nerve- 
lilaments remaining normal. There is, however, no real contradiction, as Popow 
l>elieves, between his observations and those of Gourbault, for the latter poisoned 
his animals very slowly (six months), and it is not improbable that the rapidity 
tif the poisoning had an influence upon the seat of the lesion. As already stated, 
the symptoms of plunibism may exactly simulate those of general poliomyelitis, 
and both Degerine and Leopold Stieglitz found degeneration of the motor cells. 
Karl Sobaffer believes that two sharply separated forms of degeneration of the 
nerve-centres occur in chronic lead-poisoning, — one consisting of a minutely 
granular destruction of the protoplasm, the other of the homogenization of the 
contents of the cell. 

The evidence at present indicates that lead is capable of producing 
a peripheral neuritis, and also a centric poliomyelitis, which may or 
may not coexist in an individual case; the probabilities being in 
favor of a peculiar peripheral neuritis, as the primary lesion of ordinary 
plumbic wrist-drop (see paper by Schultze, also Prevost and Binet). 
Hemorrhages into the nerve-centres sometimes occur. f There seems 
to be no doubt that lead really affects the nutrition of almost all 
of the higher tissues. In saturnine encephalopathy changes have 
been found in the ganglionic cells as well as in the neuroglia, with 
stenosis of capillaries and general shrinkage of the cortex (see O'Carroll). 
Marked alterations are not rare in the kidneys and other glandular 
organs, and general fibrosis of the blood-vessels is probably more or 
less developed in every slowly fatal case of chronic poisoning 
(case, Fisher). 

The excretion of lead with the gall is very active, but it is probable 
that it chiefly escapes from the body with the urine. The elimination 
seems to be capricious, and much affected by potassium iodide and by 
other influences. (See Melsens, Annuschat and Pouchet.) 

The treatment of chronic lead-poisoning evidently arranges itself 
under three indications: first, to prevent the ingestion of more of the 
poison; second, to aid in the elimination of that in the system; third, 
to relieve symptoms and restore lost functions. In lead colic the last 
two indications are met by purgatives, to which opium should be 
added to relieve pain. It is often necessary to use the most powerful 
drastics, such as croton oil; but senna, salts, and other of the milder 
cathartics should always be tried first. Alum, it is asserted, acts in 
some unknown way as a specific in lead colic, and from twenty to 
sixty grains of it may be given four or five times a day; but our 
experience is not favorable to its use. In the more chronic forms of 
lead-poisoning, to fulfil the second indication baths of potassium 
sulphuret should be employed, and potassium iodide be administered 

* For references, see Arch. f. Psychial. und Nervenhr., xvi. 447. 
t See Prog. M., xii. 827. 



302 GENERAL REMEDIES 

internally.* As the result of special investigation, Oddo and Silbert 
conclude that the elimination of lead through the skin in chronic 
lead-poisoning is important, that it is facilitated by injections of 
pilocarpine, and that the sulphur baths are valuable in the treatment 
of chronic lead-poisoning. The bath should be given (A. Eulenburg) 
in a wooden tub, two or three times a week, and should contain six 
or seven ounces of the salt. The patient, during the half-hour of his 
continuance in it, from time to time should be well rubbed with a 
coarse towel. On coming out he is to be thoroughly washed with 
warm soapsuds. The dose of the iodide should be from fifteen to 
twenty grains, administered after meals, in dilute solution. A case 
is reportedf in which galvanic baths were used successfully, the 
patient being placed in the bath and the positive pole of a twenty- 
eight-cell battery applied to the nape of the neck, the negative to 
the feet. When severe cerebral symptoms arise, treatment is of little 
avail, and should be largely expectant. In cases of lead-poisoning in 
which the symptoms resemble those of acute poliomyelitis we have 
used ascending doses of strychnine with most extraordinary results, 
rapidly deepening paralysis being almost at once controlled. It is 
essential that the strychnine be pushed to the point of systemic 
intolerance. It is best to administer it by the mouth, or if used hypo- 
dermically it should be given at least twice a day. It may possibly 
prove of value in other acute forms of lead palsy. 

The local use of electricity is exceedingly important to restore the 
lost function of nerve and muscle. When the faradic current elicits a 
response, it should always be employed; but in some cases the con- 
tinued current retains its power after the induced has lost all its 
influence. The rule is always to apply that current which causes 
contraction; if both fail, the continued current should be used, the 
poles being reversed at intervals of four or five seconds. The electrical 
seances should be triweekly, each lasting about fifteen minutes, and 
they should be persevered in for months. We have seen great 
improvement in a case which for the first four months yielded 
no results; indeed, long after voluntary movement had in great 
measure returned, no form of electricity would cause contraction 
of the affected muscles. 

Physiological Action. — The symptoms of acute lead-poisoning 
are chiefly due to its local irritant action, but those of chronic poison- 

* As the result of a careful series of analyses, J. D. Mann (Brit. Med. Journ., 1893, i.) concludes 
that in chronic lead-poisoning there is a great fluctuation in the elimination of lead, that potassium 
iodide has no real effect in increasing the elimination, that lead is eliminated from the intestines 
even more freely than from the urine, and that the previous contrary results obtained by investi- 
gators have been due to chance coincidences of the iodide treatment with increase of the lead 
excretions from other cause. He recommends especially general massage, and confirms to some 
extent the assertion of Tedeschi, that this massage increases remarkably lead elimination. On the 
other hand, cases are reported in which lead was not in the urine before, and was after the adminis- 
tration of the drug (see Brit. Med. Journ., 1880, ii. 1034). Moreover, John Marshall (Therap. Gaz., 
iv. 97) has shown by actual experiment that potassium iodide in solution has an action on the 
insoluble lead carbonate and phosphate, with the formation of a soluble lead compound,— double 
lead and potassium iodide; and therefore, if lead taken into the system be deposited in the tissues 
as insoluble carbonate or phosphate, these latter compounds, on the administration of potassium 
iodide, wil) be decomposed, with the production of a soluble lead compound, and consequently a 
more rapid elimination of the lead will occur. 

t L. L., 1876, ii. 53. 



ASTRINGENTS 303 

ing are of wider significance. How bhe lead is absorbed to produce 
them is uncertain, probably as an albuminate. All the compounds 
of lead and albumin as yet discovered by the chemist, are, however, 
precipitated by alkaline carbonates, and cannot, therefore, exist in 
the blood. 

The symptoms of chronic lead-poisoning are probably in great 
part secondary to the structural alteration produced by the drug, 
lead being a poison to all forms of protoplasm. Why in one case one 
set of organs should be attacked and in another case a different por- 
tion of the body is a mystery. The nephritis which is so common a 
result is no doubt connected with the effort to eliminate the poison 
from the system. 

The chief research we know upon the effects of lead upon the lower animals is 
that of Ernest Harnack, who employed the compound of lead and ethyl first dis- 
covered by Loewig. When this is injected into animals in large quantities it causes 
a rapidly fatal train of symptoms evidently due to the action of the compound 
itself. When, however, the introduction into the system has been slow, a chronic 
poisoning is produced by the lead set free in the blood and tissues. 

Under these circumstances a constant symptom in both dogs and rabbits is 
diarrhoea, due to a violently increased peristalsis, with, in the dog, occasional at- 
tacks of colic. Harnack found that in dogs the lead ethyl produces violent excite- 
ment, with chorea, convulsions, etc., evidently due to an exciting or irritant action 
upon the cerebrum, and believes that this explains the saturnine cerebral cases 
sometimes seen in man. 

The chief symptom of the poisoning in frogs was a progressive palsy of mus- 
cidar origin. The muscle became exhausted on repeated galvanization much more 
rapidly than is normal, and after death was incapable of undergoing complete post- 
mortem rigidity. The peripheral nerves appeared to have escaped entirely. The 
heart -muscle shared the fate of the voluntary muscles. The muscular action of the 
poison was excessively pronounced in rabbits, but was feeble in dogs and cats. 
Different results have, however, been arrived at by H. von Wyss, who found that 
the loss of reflex activity, etc., in the frog was not prevented by tying an artery so 
as to protect the leg from the poison, and that the protected muscle lost its power 
of responding to electrical stimulation just as fast as did the one reached by the 
lead. He concludes, therefore, that the paralysis is of centric origin. Curci is 
stated to have proved that lead exerts an irritant influence upon the peripheral 
branches and ganglionic centres of the pneumogastric. According to the researches 
of Ellenberger and Hofmeister, in the sheep toxic doses of lead greatly depress the 
elimination of urea. 

The pulse in lead colic is usually very hard and tense. Sphygmo- 
graphic studies made of it by August Frank and Ernest Bardenhewer 
have been thought to indicate a condition of general arterial spasm, 
and have given rise to the theory that the colic is caused by intestinal 
anemia from vaso-motor contraction. Harnack, however, found that 
in dogs and rabbits the lead ethyl has no action upon the vaso-motor 
system and does not produce spasm of the vessels. Moreover, he 
determined that both the diarrhoea and excessive peristalsis produced 
in dogs were arrested by atropine, which ought to promote rather than 
lessen vaso-motor contraction. Lead colic in man is probably due to 



304 GENERAL REMEDIES 

a spasmodic contraction of the intestines so powerful as to arrest 
peristalsis, and to so press upon the blood-vessels as to force the blood 
from the abdomen into the general circulation.* 

BISMUTH. 

Metallic bismuth is not used in medicine. Of the six official 
salts the citrate is not itself used except in the form of bismuth am- 
monium citrate, which differs from the other official preparations of 
bismuth in being soluble in water. It occurs in small shining trans- 
lucent scales with a metallic taste. The insoluble salts of bismuth 
are all of them heavy, odorless, tasteless powders, the subnitrate and 
subsalicylate being white, the subgallate bright yellow and the 
subcarbonate pale yellow. The subnitrate of bismuth frequently 
contains free acid and should, therefore, not be prescribed with the 
alkaline carbonates. The subcarbonate on the other hand is decom- 
posed by acids. 

There is no evidence that there is any essential difference between 
the therapeutic effects- of any of the insoluble official salts of bismuth, 
nor that any of the various new chemical compounds of this metal 
have any advantage over the official preparations. 

Official Preparations: 

Bismuthi Citras Not used internally. 

Bismuthi et Ammonii Citras 2 to 5 grains (0.13-0.3 Gm.). 

Bismuthi Subcarbonas 5 to 60 grains (0.3-4.0 Gm.). 

Bismuthi Subgallas 5 to 30 grains (0.3-2.0 Gm.). 

Bismuthi Subnitras 5 to 60 grains (0.3-4.0 Gm.). 

Bismuthi Subsalicylas 5 to 30 grains (0.3-2.0 Gm.). 

Physiological Action. — The insolubility of the ordinary salts of 
bismuth makes their absorption so slow that in the ordinary methods 
of administration they have practically no effect upon the system. 
Under certain conditions, however, they may be absorbed in large 
enough quantities to give toxic effects (see p. 305). 

It was formerly believed that the insoluble salts of bismuth were 
not dissolved at all in the alimentary canal, but it is now certain that 
they are very slowly absorbed and as slowly eliminated. Harnack 
affirms that the metal has been found by Orfila in the liver, spleen, 
and urine, and by Lewald in the milk. Bergeret and Mayencon state 
that when bismuth subnitrate is administered the metal can always 
be detected, after a few hours, in the urine. They have also discov- 
ered it in the serous exudation of dropsy, and have proved that when 
a few grains of the salt mentioned are given to rabbits, in from twenty 
to thirty minutes it can be found in the urine, kidneys, spleen, blood, 
and muscles, and even eight days after the administration can be 
detected in all the tissues. Five days after the exhibition of a gramme 

* Bardenhewer affirms that pilocarpine given hypodermically will relieve simultaneously the 
pulse and the colic. 



ASTRINGENTS 30S 

of the subnitrate to a man they found traces of the metal in the liver 
and kidneys; bul the analysis of the body of a woman dead sixty- 
two days after the ingestion of two grammes yielded negative results. 
B. S. Wood also has detected bismuth in the urine four weeks after 
its last exhibition. 

According to Feder-Mcyer the bismuth and ammonium citrate causes in rab- 
bits violent tremblings with diarrhoea, accompanied after large doses by disturbance 
of the sensibility and of coordination, tetanic cramps, altered respiration (in the 
beginning accelerated and superficial, afterwards becoming slow), continual lower- 
ing of tin- blood-pressure, and death. The same observer noticed in chronic poison- 
ing similar symptoms with albuminous urine and after death fatty degeneration 
of the liver, heart, ami renal secreting structure. Similar observations were made 
by Mory, who states that the death in mammals is the result of cardiac paralysis, 
ami that in the advanced stages of chronic poisoning, when the blood-pressure is 
very low, it is not elevated by stimulation of the splanchnic nerves nor by asphyxia. 
\Y. Steinfeld has obtained in the frog from the administration of bismuth ammonio- 
citrate and ammonio-tartrate peculiar tremblings of the voluntary, muscles with 
prolongation of contraction upon stimulation with the galvanic current, and slow- 
ing of the heart's beat, also after sufficient doses paralysis of nerves and muscles; 
effects which he attributes not to the bismuth, but to the acids of the preparations. 
He states that the proper symptoms produced by the metal appear only after some 
hours, and consist of motor excitement with reflex cries which are due to irritation 
of the medulla oblongata. In acutely poisoned mammals he noticed vomiting and 
purging, convulsions with loss of power, slowing of the pulse, and sinking of the 
blood-pressure, believed by him to be all of centric origin. In chronic poisoning 
there was loss of certainty of movement with cardiac depression followed by in- 
creasing paralysis, usually ending in death without convulsions. In his studies 
upon absorption and elimination he found that the ammonio-citrates and ammonio- 
tartrates are quickly eliminated through the kidneys, so that, as a rule, after from 
ten to fifteen hours they can no longer be found in the bloo,d, tissues, or urine. 

The discovery by Theodore Kocher that the most insoluble bis- 
muth preparations are actively antiseptic led to their use in surgery, 
and to the further discovery that when applied in very large quantities 
to extensive wounded surfaces they are capable of yielding so much 
bismuth to absorption as to produce a poisoning, which is character- 
ized by acute stomatitis, sometimes gangrenous, with a peculiar 
black discoloration of the mucous membrane, usually beginning upon 
the borders of the teeth, but spreading over the whole mouth, followed 
by an intestinal catarrh with pain and diarrhoea, and in severe cases 
with desquamative nephritis, as shown by albuminous urine and 
epithelial tube-casts.* 

Bennecke reports a case of bismuth-poisoning, ending fatally, 
in a feeble infant to whom between three and four grammes had been 
given for skiagraphic purposes. Methemoglobin was found at the 
autopsy. 

That bismuth is capable of acting as a poison in the lower animals has been 
abundantly proved by the experiments of F. Balzer and of P. Dalche and E. Ville- 
jean, which show that, whether given by the mouth or hypodermically, repeated 
iarge doses of it produce gradual failure of strength, a peculiar stomatitis, and evi- 

* For cases, see Kocher, also Petersen (Deutsches Med. Wochenschr., June 20, 1883). 

20 



306 GENERAL REMEDIES 

dences of gastro-intestinal irritation, with death from exhaustion. Balzer states 
that the stomatitis which it causes differs from the stomatitis of ptyalism 
in the tendency to rapid gangrenous change; and also that the bismuth is 
eliminated with the saliva, bile, and urine, but has a distinct tendency to 
accumulate in the tissues. 

Therapeutics. — It is stated that after the administration of bis- 
muth it may be demonstrated (by means of the Roentgen rays in the 
living animal, and by means of the microscope in animals killed) that 
the insoluble preparations of bismuth gradually spread themselves over 
the gastro-intestinal mucous membrane, and undergo a slow conver- 
sion into the black oxide of bismuth.* Experimental science, there- 
fore, is in accord with the conclusion previously reached by clinicians, 
that by virtue of their physical and chemical properties these bismuth 
preparations act as protectives to the mucous membrane, and espe- 
cially by their slow change and absorption not only exert an antiseptic 
influence, but have a peculiar persistent sedative, astringent action. 
They are, therefore, of great service in the treatment of irritations 
and inflammations of those mucous membranes with which they can 
be brought in contact. Thus, they are useful to allay vomiting depend- 
ent upon gastric irritation. In simple neuralgic gastric fain following 
eating, especially when occurring in feeble, badly nourished subjects, 
bismuth is often of great service; and even in carcinoma it may 
palliate by alleviating pain and vomiting. In pyrosis it is sometimes 
successful; in gastric and enteric catarrhs it is a standard remedy. 
In the simple diarrh&a of irritation and in the chronic diarrhoea of 
camps the bismuth preparations are often very efficient; and in the 
chronic bowel complaints of children, especially as seen in the summer 
season, given with pepsin, they are almost invaluable. Bismuth is a 
very serviceable topical remedy in the treatment of mucous inflam- 
mations and of ulcers to which it can be applied directly. Thus, in 
the beginning of a gonorrhoea, the injection every two hours of a mix- 
ture containing thirty grains of bismuth to the ounce usually brings 
immediate relief; in a similar way it may be employed in leucorrhoza 
■and in acute coryza. In Germany it has been to some extent used as 
a surgical dressing. 

Administration. — In order to get the best attainable results from 
the use of bismuth subnitrate it is necessary to vary the dose and 
method of administration. In stomachic affections from five to fifteen 
grains (0.3-1 Gm.) may be given preferably when the stomach is 
empty, in order that the bismuth may be distributed as closely as 
possible over the gastric mucous membrane. In intestinal diseases 
from fifteen grains to a drachm (1-4 Gm.) may be exhibited in capsule 
from one to two hours after meals at a time when the gastric contents 
are escaping through the pylorus. Children bear proportionately 
very large doses: thus, five to ten grains (0.3-0.6 Gm.) may be given 
to a two-year-old infant. 

* Consult Cenlralblatt f. innere Medizin, 1894, S. 2. 



ASTRINGENTS 307 

The ammonio-citrate of bismuth in small dose is acl ively si imulant, 

astringent, and, probably, germicidal. In large dose it, is a violent 
irritant. It has none of the peculiar properties which grow out 
of the insolubility of the subnitrate, but is more astringent, and 
has been used in chronic diarrhoea and in the acute diarrheas 
of relaxation. 

Bismuth Oxyiodog.vllate or Airol is a, grayish-green, non-irritating, tasteless, 
odorless powder, containing about two parts of bismuth to one part of iodine. When 
brought in contact with a surgical surface it turns red from the liberation of iodine. 
According to the studies of Carl S. Haegler it is in its bactericidal properties about, 
equivalent to iodoform, the products of its surgical decomposition being, as in the 
case of that drug, active germicides. Injected into the lower animals in doses of 
from one to three grammes per kilo, it causes clonic convulsions, with coma, nephri- 
tis and fatty degeneration of the liver. Theoretically the toxic dose should produce 
the combined symptoms of iodine- and bismuth-poisoning, but in Haegler's experi- 
ments the symptoms rather resembled those caused by bismuth, and in a case 
reported by Aemmer, symptoms of bismuth-poisoning followed the injection into 
the cavity of an abscess of nine and one-half fluidrachms of the ten per cent. 
glycerin solution. Haegler took fifteen grains of airol in the course of three days 
without the production of any disagreeable symptoms. It has been largely used as 
a substitute for iodoform on account of its lack of odor. It may be employed for the 
making of antiseptic gauze or similar dressings, or applied directly as a dry powder; 
as a salve of ten to twenty per cent, with lard or vaseline free from water, or be in- 
jected in ten-per-cent. glycerin solution in tubercular or other abscesses, or used in 
the form of suppositories made with cacao-butter in metritis, vaginitis, etc. Brun's 
paste, much used in various skin diseases and ulcerations, consists of airol one part, 
mucilage and glycerin each two parts, kaolin sufficient to make a soft paste. 

CERIUM OXALATE. 

Cerium oxalate of the U. S. Pharmacopoeia is a white powder, 
insoluble in water, alcohol, and ether, but soluble in hot diluted 
hydrochloric or sulphuric acid. It is a mixture of the oxalates of 
cerium, didymium, prsesodymium, lanthanum, and other rare earths. 
It has been employed in medicine quite largely for the relief of vomit- 
ing, especially when dependent upon pregnancy or other forms of 
uterine disturbance. Its action on the economy has not yet been made 
out, but it may be tried with some hope of success in cases of nervous 
or dyspeptic vomiting. The dose is one to three grains (0.06-0.2 Gm.), 
in pill, three or four times a day. 

ZINC. 

The salts of zinc are astringent and antiseptic. They have some 
action, not clearly defined, upon the system after absorption. Chronic 
zinc-poisoning, if it really exists at all, is very rare, and the metal 
seems to be used with impunity in cooking-utensils. 

Schlockow affirms that zinc-smelters rarely live to be over forty-five years 
of age, dying sometimes of catarrh of the bronchial or alimentary mucous mem- 
branes, or, in other cases, of a peculiar nervous affection, which commences with 



308 GENERAL REMEDIES 

burning superficial pains, exalted sensibility and reflex activity in the legs, and 
afterwards puts on still more clearly the features of myelitis; and A. Sacher finds 
that intravenous injection of very large doses of zinc salts produces paralysis of 
the voluntary muscles. 

Official Preparations: 

Zincum Not used internally. 

Zinci Acetas 2 grains (0.12 Gm.). 

Zinci Bromidum 2 grains (0.12 Gm.). 

Zinci Carbonas Precipitatus External use. 

Zinci Chloridum External use. 

Zinci Iodidum 1 grain (0.06 Gm.). 

Zinci Oxidum 2 grains (0.12 Gm.). 

Zinci Phenolsulphonas 2 grains (0.12 Gm.). 

Zinci Stearas External use. 

Zinci Sulphas As an emetic 15 to 30 grains (1-2 Gm.). 

Zinci Valeras 3 grains (0.2 Gm.). 

Unguentum Zinci Oxidi (20 per 

cent.) External use. 

Unguentum Zinci Stearatis (50 per 

cent.) External use. 

Liquor Zinci Chloridi (50 per cent.) Not used internally. 

Zinc Sulphate. — White Vitriol occurs in irregular white masses, 
the pure zinc sulphate in minute, transparent, four-sided, prismatic 
crystals, which effloresce slightly in dry air, and are soluble in 0.53 
part of water at 77° F. and in 0.2 part of boiling water, also soluble 
in about three parts of glycerin; insoluble in alcohol. The taste is 
styptic and peculiar. 

Zinc sulphate is, in weak solution, a stimulant astringent; in 
concentrated form an active irritant. Its chief value is as a rapidly 
acting emetic, especially in cases of poisoning. Dose, thirty grains 
(2 Gm.). In doses of one grain (0.06 Gm.), it has been given in pills 
as a stimulant astringent in chronic diarrhoea with ulceration. 

Toxicology. — Zinc sulphate in large doses acts as an irritant 
poison, producing violent vomiting, colicky pains, diarrhoea, pros- 
tration, etc. The symptoms which it causes are almost identical 
with those produced by the corresponding salt of copper. Alkalies 
and their carbonates are the chemical antidotes to it, producing 
insoluble precipitates. Eggs and milk should also be exhibited, and 
the symptoms treated as they arise. 

Zinc Oxide. — Commercial zinc oxide is a snow-white powder, 
obtained by burning the metal in the air. It should be used only in 
pharmacy. The pure oxide is a white or 3'ellowish-white powder, 
insoluble in water or alcohol, but soluble without effervescence in 
dilute acids. 

Therapeutics. — Zinc oxide is used externally as a mildly astringent, 
slightly stimulant, and desiccant application in skin diseases and to 
ulcers. When given continuously in small doses it is believed to act 
as a tonic and alterative upon the nervous system. It has also been 
commended as an astringent in chronic catarrhal diarrhoea of adults 



ASTRINGENTS 309 

and infants, and has been largely used in epilepsy and in chorea. 
Dose, one-half to two grains (0.03-0.13 Gm.). The ointment is 
useful in various skin diseases. 

Zinc Carbonate. — Hydrated zinc carbonate is intended to replace the old 
impure native carbonate, calamine. It is made by precipitating the zinc sulphate 
by the sodium carbonate. It is a white powder, closely resembling in its medical 
properties zinc oxide. 

Zrac Acetate. — Zinc acetate occurs in white, micaceous crystals, which efflo- 
resce in a dry atmosphere and are very soluble in water. The taste is astringent 
and metallic. The zinc acetate resembles in its physiological and therapeutic quali- 
ties die sulphate, but is probably somewhat less active. It is chiefly used in collyria 
(one to two grains to one fluidounce), and as an injection (one to twenty grains 
10 one fluidounce) in ijonorrhaia. 

Zinc Bromide. — This is a white or nearly white deliquescent powder of a 
saline metallic taste. In full doses it is an irritant emetic but has been chiefly 
used in epilepsy. Its value is doubtful. 

Zinc Chloride. — Zinc chloride occurs in white or nearly white 
porcelain-like masses freely soluble in water. It is used as a caustic 
and disinfectant. 

Zinc Iodide. — A white or nearly white deliquescent powder which 
deserves no place in the U. S. Pharmacopoeia. 

Zinc Phenolsulphonate. — The sulphocarbolate of zinc occurs 
as efflorescent, colorless crystals, freely soluble in water. It is largely 
used as an intestinal antiseptic but is probably of no value. 

Zinc Stearate. — This is a white powder with a slight fatty odor, 
insoluble in water, alcohol, or ether. It is used as a dusting powder 
in similar conditions to those calling for zinc oxide. 

COPPER. 

The only official salt of copper is the sulphate. This occurs in 
blue, transparent, slightly efflorescent, rhomboidal prisms, or their 
fragments. It dissolves, at 77° F., in about 2.2 parts of water and 
in 0.5 part of boiling water; almost insoluble in alcohol. With am- 
monia its solution precipitates a bluish-white cupric hydrate, which 
redissolves when an excess of the alkali is added, forming a rich deep 
blue solution. 

Physiological Action. — In very dilute solution the copper sul- 
phate acts locally as a stimulant and mild astringent; in a more con- 
centrated form it is an irritant; in powder it is a very mild caustic, 
which is scarcely capable of destroying sound tissue. The salts of 
copper in sufficient amount are poisonous to all forms of protoplasm. 
Coupin found that 0.0055-per-cent. solution of soluble salt of copper 
will prevent germination of wheat; that copper compounds affect 
violently the general nutrition in animals is shown by the production 
of fatty degeneration by them (see Ellenberger and Hofmeister). 



310 GENERAL REMEDIES 

According to Falck, the cupric sulphate causes in the lower animals 
great depression of temperature, with progressive general paresis, 
ending in death, apparently from failure of respiration. When the 
copper salt was given hypodermically, vomiting was not produced; 
although when it was exhibited by the mouth, emesis was very 
violent and persistent. 

Cupri Sulphas | to \ grain (0.008-0.015 Gm.); 

as an emetic 3 to 5 grains (0.2-0.3 Gm.). 

Therapeutics.— Cupric sulphate is occasionally used for its local 
effect in chronic enteritis and colitis, with ulceration, but is rarely of 
value. It was at one time much employed in the treatment of organic 
nervous diseases, but has fallen into deserved desuetude. Forty years 
ago Mendini recommended it in the treatment of chlorosis with 
amenorrhoea, a use which has been revived from time to time and 
has recently been commended by Liegeois. A. F. Price claims that 
cupric sulphate in doses of one-thirtieth of a grain three times a day 
greatly enhances the power of the mercurials in syphilis. 

The chief value of the so-called blue stone is as an external appli- 
cation. When applied in solid form to ulcers, it destroys flabby 
granulations and exerts a powerful excitant influence. Its solution 
acts more feebly, and is sometimes employed as a dressing for indo- 
lent ulcers, but more frequently as a stimulant and alterant to mucous 
membranes, as in granular conjunctivitis and urethritis. 

In 1904 Moore and Kellerman of the U. S. Department of Agri- 
culture stated that copper sulphate even in minute quantities is 
capable of destroying both algae and typhoid bacilli. According to 
Gildersleeve 1 part in 1,000,000 is sufficient to kill all typhoid germs 
in water in three hours although other microorganisms seem more 
resistant. This property depends probably on the dissociation of 
the ions, for metallic copper seems to be more efficient than any of 
its salts. Stewart found that water inoculated with typhoid bacilli 
and kept in copper vessels contained none of these organisms after 
three hours and comparatively few of the other forms of bacteria, 
and Kraemer has shown that copper foil placed in the water has the 
same effect. It does not seem probable that the minute quantity 
of copper present in these circumstances (about 1 part to 4,000,000) 
can exercise any very deleterious effect on the system, especially as 
much of it becomes united with the organic matters and precipitated. 
When large amounts of foreign substances are present in the water 
copper is so much less efficient in its germicidal powers, that 
according to both Fowler and Doty it is of no practical value. 

Toxicology. — The symptoms of acute copper-poisoning gener- 
ally come on in about a quarter of an hour, but may be postponed 
for from one to two hours. They consist of violent vomiting and 
purging, accompanied by the very severe colicky pains. The matters 
vomited are greenish or bluish, the stools glairy, mucous, and at 
times bloody. There is a very strong taste of copper in the mouth. 



ASTRINGENTS .ill 

and often constant expectoration; excessive salivation and bronchia] 
secretion are stated by Galippe to be characteristic. Death may 
OCCUr in a few hours, preceded by convulsions, paralysis, delirium, 
anesthesia, and other symptoms of great nervous disturbance, seem- 
ingly as the result of a direct action of the poison upon the nervous 
system. Sometimes a tendency to syncope is very marked, and as 
both L. Schwarz and W. Pilehne have found that toxic; doses of 
copper salts paralyze the heart in the lower animals, cardiac death 
probably occurs in human poisoning. The urine is usually lessened 
or suppressed. Black urine, due to the presence of hemoglobin with- 
out unaltered blood-corpuscles, has been noted; in this case, after 
death all the tissues were found stained with altered blood, and 
evidently destruction of the blood was an important factor in the 
fatal result;* fatty degeneration of the liver was also found. If the 
patient survives for twenty-four hours, jaundice nearly always shows 
itself. After this, profound depression with nervous symptoms may 
develop and end in death; but not rarely a favorable issue results, 
in which case the symptoms of gastro-intestinal inflammation with 
fever develop themselves. The copper is said to be eliminated more 
freely with the salivary and intestinal secretions than with the urine 
(Galippe). 

As the action of the cupric sulphate is exceedingly rapid, any 
antidote to be of avail must be given at once and act quickly. In 
the poisoning milk, eggs, or other albuminous substance should be 
exhibited immediately, freely, and repeatedly. f Soap or a fixed 
alkali may be used. The yellow prussiate of potash, when pure, is 
harmless, and precipitates instantly an insoluble compound of copper 
from solutions of its salt. When it is to be had in time, it may there- 
fore be used as an antidote to the sulphate. The treatment of copper- 
poisoning after the administration of the antidote consists in meeting 
the indications as they arise; opium should be used freely. When 
death occurs, the results of gastro-intestinal inflammation are usually 
found; sometimes the intestine has a decided bluish tint, and occa- 
sionally submucous ecchymoses occur. In exceptional cases, it is 
said, there are no evidences of inflammation in the alimentary canal, j 
Fatty degeneration of the liver has been noted in man. 

There has been much discussion as to whether there is or is not a 
chronic copper-poisoning among workers in that metal. 

The chief symptoms which have been described as present are coppery taste 
in the mouth, gastro-intestinal irritation with pain, anemia, progressive emacia- 
tion, cough, and nervous disturbances with tremors. The green discoloration upon 

V. Y. M. ft., xxi. 567. 

t No time should be lost in attempting to separate the yolk from the white of the egg, but the 
egg should be broken into a bowl as quickly as possible, a little water added, and the whole stirred 
up and exhibited. 

X For a fatal case of repeated poisoning by copper, with much information of value to chemical 
experts, see La France Med., September, 1874, abstracted in Hall-Yearly Compendium. January, 
1875. Bournevette and Yvon (Revue Scientifique, 1874, 859) found two hundred and ninety-five 
milligrammes of metallic copper in the liver of a woman who had taken the ammouiacal sulphate 
three months previously. Minute quantities of copper exist, in the normal human body (Bull. 
Therap., xciii. 88). 



312 GENERAL REMEDIES 

the gums or teeth, which was first pointed out by Clapton, has been noted by Taylor, 
by the Committee of the London Clinical Society, and various other observers. It 
is, however, not constant, and may exist in persons who show no other evidences of 
poisoning. According to Kurth, it really consists of a greenish or olive discolora- 
tion on the front of the teeth, and is due to the staining of the tartar, since when the 
teeth are perfectly clean there is no staining. It is probable that most, if not all, 
of the symptoms of the chronic poisoning noted in workers in copper are due to the 
local action of the copper dust upon the various mucous membranes, an explanation 
which is rendered more probable by the fact pointed out by Kurth, and also by Lewin, 
that workers in copper often have their hair colored green. 

When copper is given to the lower animals in continuous sufficient dose it 
produces loss of appetite, failure of digestion, diarrhoea, and other evidences of 
gastro-intestinal catarrh; with marked evidences of disturbances of the nutrition, 
such as emaciation, failure of the heart, and with a progressive paralysis and failing 
respiration ending in death. After death alterations of the blood and wide-spread 
fatty degeneration have been noted by numerous observers.* According to Von 
Bokay the muscles are very early affected, cloudiness of their protoplasm and dis- 
appearance of their cross-striation coming on. The liver and kidneys, however, are 
especially attacked: in the beginning there are hyperplasia of the connective tissue 
and subacute nephritis, followed by fatty degeneration and finally atrophy. 

Although Galippe and Burcy and also Ducom affirm that copper 
is almost without influence upon dogs, and Galippe fed himself for 
one month on food containing a large amount of copper without 
causing any symptoms of intoxication, it is probable that while very 
minute quantities of copper may be taken internally habitually with- 
out producing injury, larger doses may slowly and insidiously work 
out fatal consequences. The matter is important because the metal 
is habitually used in the canning of vegetables, French peas, beans, 
etc., owing their attractive color to their treatment with copper, 
which can be chemically recognized in them. 

The possibility of injury from such food has been repeatedly investigated by 
French and Belgian commissions, and the general verdict has been that no harm is 
produced. The fact that twenty millions of cans of these food-articles are con- 
sumed every year, and that after thirty-six years' continuance of the custom it lias 
not been clearly established that harm is done, indicates that in the amount used 
the vegetables containing copper are not poisonous. It is plain that the freedom 
from injury depends upon the minuteness of the amount of copper ingested; the 
Italian law does not allow more than 0.05 gramme of copper per kilo of food, but 
the researches of Tschirch would indicate that a food containing this amount of 
copper, if very freely taken, might do harm.f 

SILVER. 

Probably all the salts of silver are more or less actively germi- 
cidal (see page 655) in their influence as well as astringent. Three 
salts of silver are recognized by the Pharmacopoeia: the cyanide, 
the nitrate and the oxide. 

Silver cyanide is used only for the manufacture of hydrocyanic 
acid; never as an internal remedy. 

* Falck (Deutsch. Klinik, 1859, xi.), Ellenberger and Von Hofmeister {Arch. Wissen. Prakt. 
Thierheilk., s. 228), W. Filehne (Deutsch. Med Wochen., 1893, xxi.), De Moor, Von Bokay (Pester 
Med.-Chir. Presse, 1897, 33), Baum and Seeliger (Archiv f. Thierheilk., 1897, xxiii., 1898, xxiv.), 
and Trolldenier (Archiv /. Thierheilk., 1897, xxiii.). 

t For discussion upon the subject, see De Moor (Archives de Pha.Tmacodyna.mie, 189">, i.) and 
Tschirch (Toxicologic und Hygiene, Stuttgart, 1893). 



ASTRINGENTS 313 

Silver oxide is a dark in-own powder almost insoluble in water 
and readily reduced by the action of light to metallic silver. It is 
comparatively little used. 

Silver nitrate exists in translucent shining rhombic crystals with 
a styptic metallic, corrosive taste. It is freely soluble in water, and 
moderately soluble in alcohol. For external use the crystals are 
melted and run into moulds, where they harden into round, grayish, 
brittle sticks, about the size of a goose-quill, and having a radiated 
crystalline fracture. These constitute the official Argenti Nitras 
Fusus. As only the pure salt will make well-formed crystals, the 
impure products are always manufactured into the fused nitrate, 
which should therefore not be employed internally. When silver 
nitrate, either in substance or in solution, is exposed to the conjoint 
influence of light and of even a minute portion of organic matter, 
it turns black, and is converted into an insoluble substance, which 
has been believed to be metallic silver, but is more probably an oxide. 
For this reason the white stains which it first makes when applied 
to living tissues soon blacken. 

Official Preparations: 

Argenti Cyanidum Not used internally. 

Argenti Nitras £ grain (0.015 Gin.). 

Argenti Nitras Fusus External use only. 

Argenti Nitras Mitigatus External use only. 

Argenti Oxidum 1 grain (0.06 Gm.). 

Physiological Action. — Local Action. — Silver nitrate coagulates 
albumin, and, when applied in its pure state to living tissues, acts 
as a caustic, coating them over with a white almost membranous 
film. The caustic action is, however, not a deep one, because pene- 
tration of the salt into the tissues is soon prevented by the thick 
and tough skin or stratum which is formed. When applied in a 
dilute solution it acts as an astringent, constringing the vessels and 
overcoming relaxation. Its local action, however, is not simply that 
of an astringent, but is certainly peculiar and apparently alterative 
to nutrition. It is also a very active germicide. 

Absorption and Elimination. — It is evident that in the stomach 
silver nitrate cannot long maintain its integrity. Bogolowsky has 
found that when the nitrate is added to a peptone it is readily dis- 
solved, and that the solution formed does not coagulate albumin.* 
That in this or in some other analogous form silver is absorbed is 
proved by its having been found in various internal organs and by 
the discoloration which follows its protracted use: argyria of authors. 
When it is exhibited for a long continuous period, the skin often 
acquires a peculiar bluish slate color, which may become very dark, 
and in decided cases the conjunctiva and even the mucous membrane 
of the mouth are involved. The silver is found in all the tissues of 

* For recent studies of this character, see Isidore Neumann (toe. cil.), also A. von Fragstein 
(Berlin. Klin. Worker,.. 1877, 294). 



314 GENERAL REMEDIES 

the skin below the rete Malpighii* (Frommann, Riemer, Neumann). 
E. Harnack asserts that in all recorded cases of argyria at least thirty 
grammes of the salt have been taken. The staining of the skin is 
always preceded by a dark discoloration of the mucous membrane 
of the mouth and gums. Both Heller and Orfila failed to detect silver 
in the urine of animals taking it; but probably it is eliminated, though 
slowly and in very small quantities, by the kidneys. 

General Effects. — As silver is never given for an immediate thera- 
peutic action, its acute physiological action is of less interest to the 
therapeutist than to the toxicologist, and the detailed symptoms of 
its poisoning are considered under the head of toxicology. In general 
these symptoms consist of those of gastro-enteritis with violent 
disturbance of the nervous system, due to a direct action of the poison 
upon the cerebrum and the spinal cord.f Although the circulation 
is profoundly affected, death appears to take place from centric 
paralysis of respiration. 

By an elaborate series of experiments Charles Rouget has shown that upon all 
animals from a crab to a dog the soluble salts of silver act as a poison, causing in 
mammals vomiting and purging, and in them and the lower animals violent dis- 
turbance of the motor functions, as shown by paralysis and convulsions, and of the 
respiration, ending finally in death by asphyxia. This is in accord with the obser- 
vations of other investigators. Rabuteau and Mourier affirm that the almost instan- 
taneous death which Charcot and Ball first noted, as following the injection of a 
large dose of silver nitrate into the veins, is due to a direct paralyzing influence of the 
drug upon the muscle of the heart. Rouget has never seen this form of death fol- 
low the hypodermic or internal administration of the poison, the heart always 
continuing to beat for a greater or less length of time after the cessation of 
respiration, and also retaining its irritability. 

As already stated, both convulsions and paralysis are present in acute silver- 
poisoning. The convulsions are severe, generally tetanic, and according to Rouget 
are plainly reflex. A peculiarity noted by Rouget is the persistance of the convul- 
sions after the complete abolition of voluntary movements. Curci affirms that 
they are due to excitation of the motor tract of the cord, and that this is preceded 
by a similar influence upon the sensory tracts. 

The death is due, in argyria, to cessation of the respiration; Rouget even states 
that he has witnessed the suspension of the latter function in the frog while the 
activity of the reflex movements was much beyond normal. In the dog and in the 
full-grown cat this asphyxia is accompanied by an outpouring of mucus in the lungs, 
pulmonary congestion and cedema being found on post-mortem examination. Two 
theories have been propounded as to the cause of the asphyxia: one, that it is 
simply due to the choking up of the lungs by the congestion and the excessive 
secretion whose origin is an altered state of the blood; a second, that both the 
asphyxia and the lesions in the lungs have their origin in a direct action of the 
poison upon the nerve-centres. 

* In an elaborate study of the organs of a case of argyria, Riemer detected the silver in the 
glomerules of the kidney, the intirna of the aorta, the choroid plexus, and the mesenteric glands. 
He believe? that it is never deposited inside the cells, and that the silver preparation is reduced in 
the intestines, and the fine particles of the silver carried in the blood and lymph. Gerschun (Arbeiten 
aus Physiolog. hist, zu Dorpal, x.) coincides with Riemer in affirming that the silver is deposited 
outside of the cells, but O. Loew (Pfliiger's Archiv, xxxiv. 603) asserts that it occurs inside of the 
renal endothelial cells. Jahn (Beitrilge z. Patholog. Anat., xvi.) states that the unstriated muscular 
fibres and the elastic tissue have a special power of reducing silver. 

t Orfila and other of the earlier observers experimented upon it by injecting it directly into 
the veins of animals. When exhibited in this way, it must, by coagulating the albumin of the 
blood, produce thrombi, to which the subsequent symptoms are in greater or less measure to be 
ascribed. This method of experimentation can, therefore, throw but Tittle light upon the action of 
silver nitrate when taken into the stomach. 



ISTRINGENTS 315 

The 6rs1 view has been especially supported by Krahmer and by Rabuteau and 

Mourier. Unfortunately, we bave not seen the original papers of these physieians; 
but, according to Rouget, the basis of the argument of Krahmer •« simply the eechy- 
moses which lie found in horses de:ul of the poison, while that of Rabuteau and 
Mourier is the fluidity of the blood after death, and the existence in it of granules 
which, on account of their solubility in ammonia, were believed to be silver chlo- 
ride. The French observers were, however, almost certainly mistaken in their 
belief that these granules were silver chloride, since ammonia dissolves heniatin 
as freely as it does the chloride. 

In 18(54 Charcot and Ball made a series of experiments in which a silver salt 
that did not coagulate albumin was injected directly into the blood. They noted 
not only the respiratory embarrassment, but also that the hinder extremities were 
suddenly paralyzed, and concluded that both the asphyxia and the lung trouble 
were due to an affection of the central nervous system. In 1869 Bogolowsky, of 
Moscow, studied the action of a peptone of the nitrate when used hypodermically. 
He found, on examination of the blood of a poisoned animal, that the spectrum 
analysis betrayed nothing abnormal; that the red corpuscles appeared paler and 
their outline more delicate than normal; and that the white corpuscles were natural. 
On the other hand, Rouget examined microscopically the blood of animals poisoned 
with silver nitrate, and found it perfectly normal. The only conclusion to be drawn 
from all this seems to us to be that at present there is no proof whatever that the 
symptoms of acute silver-poisoning are due to alterations in the blood; that the 
embarrassment of respiration is not due to local lesions in the lungs is abundantly 
shown by the experiments of Rouget, who found that while in all animals these 
respiratory symptoms are very prominent, in only a few species are decided pul- 
monic lesions found after death. From ah these facts we think it highly probable, 
if not altogether certain, that the theory propounded by Charcot and Ball is correct. 
That the motor disturbance is centric, not peripheral, in its origin, is shown by the 
fact noted by Rouget, that the muscles and nerves preserve their excitability after 
the arrest of the respiration. 

We know of very few, if any, cases of chronic poisoning with 
silver salts in man (see foot-note, page 318); the following summary 
epitomizes the results of chronic poisoning in the lower animals. 

The action of the drug when exhibited continuously for a length of time in 
large doses has been investigated by Bogolowsky upon dogs and rabbits. He found 
that it produced loss of appetite, wasting, slight lowering of bodily temperature, 
diarrhoea, diminution of the quantity of urine passed, with increase of its specific 
gravity and often with the presence of albumin, and transitory paralysis. How 
far some of these symptoms were due to the direct constitutional action of the 
poison and how far to derangement of the digestion dependent upon its local in- 
fluence is perhaps an open question. The local action was avoided, however, as 
much as possible, by the use of an albuminate or of the double phosphate of silver 
and sodium, which does not coagulate albumin. Comparative examinations of the 
blood showed that the hemoglobin was diminished by more than one-third. The 
blood was also rendered very aplastic, as was betrayed by the constant tendency to 
the formation of ecchymoses. As some one has suggested that the silver in these 
cases replaces the iron of the blood-corpuscles, Bogolowsky made a chemical 
examination of the latter, but failed to find any traces of silver in them, — no doubt 
because it was not there. The solid tissues were found, after death from chronic 
argyTia, to be in an advanced stage of degeneration, which especially affected epi- 
thelial structures. The first change was swelling and opacity of the cells, with 
obscuration of the nucleus. After this came fatty degeneration, fatty globules in 
the cell, destruction of nucleus, and finally of the cell itself. The liver and kidneys 
were profoundly influenced, as was also the muscular structure, especially of the 
heart. These results obtained by Bogolowsky have been in the main corroborated 
by A. V. Rozsahegzi. 



316 GENERAL REMEDIES 

Therapeutics. — The results of the chronic poisoning by silver 
are in every way so closely analogous to those produced by anti- 
mony, arsenic, copper, and other metallic poisons as to show that 
silver belongs to that class of drugs which in some way markedly 
affects the general nutrition. It cannot, however, be called an alter- 
ative, as at present we know of no application of its power to the 
needs of practical medicine. 

The only advantageous use of silver in therapeutics is for its 
local action either upon the surface of the body or upon those mucous 
membranes that can be reached directly by the drug. 

As a simple caustic, the salt may be used whenever a superficial 
action only is required: for reasons already given (page 313), it is 
useless whenever it is necessary to produce a deep eschar. As a 
caustic alterative, it is applied in solid form to many ulcerated surfaces, 
for the purpose of destroying superficial diseased tissue and of sub- 
stituting, when the eschar separates, a health}' for an unhealthy 
action. As an antiphlogistic, silver nitrate acts not only as an astrin- 
gent, but also as a germicide. In the various inflammations of the 
mucous membranes, such as conjunctivitis, faucitis, laryngitis, ure- 
thritis, etc., it is used very frequently, not only in the stage of relaxa- 
tion, but also in the beginning of the attack. In conjunctivitis, the 
solution employed should not, under ordinary circumstances, be 
stronger than one or two grains to the ounce; and it should not be 
used at all if any corneal ulceration exists, since a deposit of silver 
is liable to occur and to produce opacity. In faucitis, the strength 
of the solution may vary from thirty to sixty grains to the fluidounce. 
In ordinary cases of sore throat, the application once a day or every 
alternate day is generally sufficient. It is best made by means of 
a good-sized camel's-hair brush, each part of the inflamed surface 
being distinctly touched, and not the whole simply daubed or slopped 
over by means of a very large brush or a sponge probang. In severe 
cases it may be necessary to use the solution twice a day. Even a 
saturated solution can scarcely be looked upon as caustic to the more 
robust mucous membranes. 

Carl Seiler states that while solutions of silver nitrate of less than sixty grains 
to the ounce cause pain when applied to the throat, solutions of one hundred 
and twenty to two hundred and fifty grains act as local anesthetics, relieving 
soreness, and usually arresting acute inflammations at once, if applied in the first 
twenty-four hours, before inflammatory exudation has occurred. 

In laryngitis, the solution may contain from ten to twenty grains 
to the ounce, and should be applied with a brush by the aid of the 
laryngoscopic mirror. An attack of urethritis may sometimes be 
aborted in its forming stage by the injection of a strong solution 
(twelve grains to one fluidounce) of the salt; but the practice is of 
doubtful expediency, since when it fails it greatly aggravates the 
trouble. When chronic gonorrhoea is strictly localized to a small spot 
in the posterior urethra, instillation of from five to ten minims of 



ASTRINGENTS 3H 

a solution of t ho strength of five to ten grains to the fluidounce is 
often serviceable. When the inflammation is more diffused, irriga- 
tion with a weaker solution is preferable; at first I to 5000 may be 
employed, and the strength gradually increased to even 1 to f)00. 

Applied to the skin of the whole finger, silver nitrate will sometimes 
abort a commencing felon, or, applied to the scrotum, an epididymitis. 

Internally, silver nitrate is exceedingly useful in stomachic and 
to a less extent in enteric diseases, exerting no doubt a purely local 
influence. In that form of dyspepsia characterized by the vomiting 
of large (plant ities of yeasty fluid, it has yielded in our hands better 
results than any other remedy; and the same may be said of chronic 
gastritis and of gastric ulcer. The rules of administration are identical 
in these three diseases. In the first place, regulation of the diet is 
imperative: if the case be a bad one, all eating of meals should be 
suspended, and the patient receive every two or three hours a cup 
of sweet milk, with sound toasted bread broken up and thoroughly 
softened in it. In order to wash off as much as possible the mucous 
membrane of the stomach, and to neutralize the acids of the stomach, 
forty-five minutes before the meal fifteen to twenty grains of sodium 
bicarbonate should be exhibited in a tumblerful of hot water, and 
ten minutes later a quarter of a grain of silver nitrate should be given 
in pill form. The use of cold water at meals should be absolutely 
forbidden, and in very serious cases, when all food is rejected by the 
stomach, it is sometimes advisable to allow absolute rest for two or 
three days to that viscus, the patient being fed by the rectum, and 
only a little water and pills of silver with opium being taken by the 
mouth. Under these circumstances, the return to the usual method 
of taking food must be very gradual, at first only a tablespoonful 
each of milk and of lime-water being administered every hour. In 
chronic enteritis or colitis, silver nitrate is sometimes of service, 
especially if there be ulceration. 

For its constitutional effects silver nitrate is used solely in diseases 
of the nervous system. It was formerly give*ti in epilepsy, but it has 
passed out of use. In chronic inflarmnations of the spinal cord, whether 
affecting chiefly the posterior columns and constituting locomotor 
ataxia, or the anterior and giving rise to paraplegia, it is still 
employed, but is of doubtful value. 

Toxicology. — The symptoms produced by the ingestion of 
large doses of silver nitrate are partly gastro-intestinal and partly 
cerebrospinal. In some instances the one series of phenomena pre- 
dominate, in others those of the other class. In a case* at the Hopital 
St. -Louis in 1839 the symptoms were insensibility, violent convulsions, 
dilated pupils, and, when consciousness was partially regained, intense 
o-astric pain: complete restoration of consciousness did not occur 
until eleven hours after admission, and the coma returned at intervals 
during several days. 



Beck's Medical Jurisprudence, 18(13, i. 675. 



318 GENERAL REMEDIES 

Vertigo, coma, convulsions, great muscular weakness, and paral- 
ysis, with intense disturbance of respiration, are in these cases the 
manifestations of disturbed innervation, while the abdominal symp- 
toms are those of gastro-enteritis. The diagnosis can generally be 
made by the discolorations of the lips and skin — at first white, after- 
wards black — and by the blackish or brownish vomit; when the 
customary antidote has been given, both vomit and stools are gener- 
ally white and curdy. After death the stomach and bowels are found 
corroded, often ecchymosed and with patches of a white or grayish 
color. Poisoning by silver nitrate is not common, and we know of 
but three fatal cases, — one in 1837 (Taylor), one in 1861, a woman 
killed by fifty grains in solution in divided doses, and one in 1871, 
a child destroyed by a piece of the solid stick three-quarters of an 
inch long, in spite of the use of the antidote (Scattergood). 

The treatment consists in the administration at once of large 
amounts of common salt, alkaline carbonates, or soap, — the chemical 
antidotes, — the constant use of large draughts of milk, and the 
meeting of symptoms as they arise. 

The fatal dose of silver varies very much, according, no doubt, to 
the presence of substances capable of decomposing it in the stomach. 
Thirty grains have killed, and recovery has taken place after the 
ingestion of an ounce (case, Husemann). 

Chronic argyria, or discoloration of the skin by silver, is usually 
unaccompanied by disturbances of health, although in severe cases 
the discoloration affects not only the skin, lips, gums, and sclerotic, 
but even the internal organs, such as the liver, spleen, and kidneys. 
It is therefore not due, as has been thought, to the silver chloride, 
since the latter becomes dark only under the influence of the light, 
but to a deposition of silver itself or of its oxide.* 

S. Krysinski found the granules in almost every tissue of the body, and states 
that they are an organic compound of silver, the exact nature of which has not yet 
been determined. The minute quantity of the metal present is shown by the analy- 
sis of Versmanns, who in 14.1 grammes of dried liver found only 0.0068 gramme 
of metallic silver (0.047 per cent.), and in 8.6 grammes of dried kidney 0.053 gramme 
(0.61 per cent.). Greater or less success has been asserted for various treatments 
in argyria, but in general they are equally futile. 

Rogers states that blistering will lighten the color very much, 
and Eichmann asserts (Husemann) that he has cured two cases by 
the use of potash baths and of soap baths, each four times a week. 
The older authorities commend the use of potassium iodide internally. 
L. P. Yandell has reported two cases in which large doses of the iodide 
were given for many months for syphilis, and the mercurial vapor- 
baths used at the same time for the same purpose, with the result of 
a complete cure of the argyria. The fading was gradual. 

* According to Rozsahegzi, Hermann has seen one case in which preceding the deposition 
of the silver there were malaise, emaciation, failure of memory, singing in the ears, deafness, and 
spasms of the ocular muscles. 



ASTRINGENTS 319 

Administration. — The silver nitrate should always be given 
in pill, and, when it is desired to obtain its constitutional influence, 
after meals, during the process of digestion; but when its local action 
on the stomach is required, it should be administered one or two 
hours before meals; and if the intestines are to be reached, the pill 
should be enclosed in two thick capsules. The administration of 
silver nitrate should not extend over a longer time than two months 
without a protracted intermission. 

Albargin. Gelatose Silver. — This compound of silver and gelafose is a yel- 
lowish, bulky powder, dissolving readily in cold or warm water, and containing 
fifteen per cent, of silver. It affects albumin slowly, but may be used with cocaine 
provided the double solution be freshly prepared at the time of administration. 
It should be kept in amber-colored bottles. It was introduced by Bornemann, to 
be used in a one- to two-per-cent. aqueous solution in gonorrhoea. 

Silver Acetate. — This has been especially recommended by Zweifel in a 
one-per-cent. solution for the treatment of ophthalmia in new-born children. 

Silver Citrate. Itrol. — A dry, odorless powder, soluble with difficulty in 
water, has been recommended as intensely poisonous to the gonococcus and non- 
irritant to the urethral membrane. The injection of from 1:4000 to 1:8000 solution 
is said to produce no pain even in acute gonorrhoea, and may be practised four times 
a day. The remedy has also been used in chronic cystitis. 

Silver Lactate. Actol. — This substance is soluble in fifteen parts of water, 
and may be used in very strong or saturated solution for the disinfection of infected 
wounds. It is decomposed at the point of application, but is said to form soluble 
compounds, so that it is able to find its way deeply into the tissues. One gramme 
has been given hypodermically without serious symptoms, except some burning. 
The application of the pure powder to an affected surface is asserted to produce 
only moderate and brief pain. 

Argentol. — A yellowish powder which readily splits up into oxyquinoline 
and metallic silver; it has been recommended by Cipriani as efficient, in diarrhoea, 
as an astringent, intestinal antiseptic of which fifteen grains (1 Gm.) may be given 
safely in twenty-four hours, if necessary. It has also been used surgically in the 
strength of 1 to 300 to 1000. 

Argyrol. Silver Vitellin. — This albuminous compound of silver occurs in 
dark-brown hygroscopic scales, very freely soluble in water, and containing about 
thirty per cent, of silver. It has been largely used, but both Derby and Marshall 
and Neave have found that it possesses no germicidal properties. 

Largin. — This compound of silver and albumin is a whitish-gray powder, 
soluble to about ten per cent, in water, freely soluble in blood serum, not precipi- 
tated by albumin, and containing 11.1 per cent, of silver. It has great penetrating 
power when brought in contact with tissue, and has been highly praised by a num- 
ber of German clinicians as a germicide in the treatment of gonorrhoea both in men 
and women. It is used in strengths of one-fourth to four or five per cent. In infec- 
tious conjunctivitis and in catarrhal corneal ulcers, Welander especially commends 
the use of gelatin tablets containing one per cent, of largin. 

Silver Stjlphocarbolate. Silberol. — Introduced by Zanardi as a substitute for 
silver nitrate, this substance has been considerably used in gonorrhoea, and as a sur- 
gical germicide, especially in connection with the eye. It is asserted that the two-per- 
cent, solution is well borne by the conjunctiva, and that when used as a substitute 
for silver nitrate silberol must be employed in twice as concentrated a solution. 



32U GENERAL REMEDIES 

Soluble Silver. Colloidal Silver. Collargol. — This allot ropic form of silver, 
discovered by M. Carey Lea in 1891, occurs as a bluish or green-colored mass. I' 
makes with water a deep red solution, which is precipitated by the addition of salt 
solutions. Soluble silver was originally employed by Crede as a non-poisonous ger- 
micide, to be used for internal medication in various affections, such as septicemia, 
diphtheria, and tuberculosis. At first he exhibited it by inunctions, forty-five 
grains at one time for the adult, but later gave five to ten grammes of the one- 
per-cent. solution hypodermically or intravenously. The harmlessness of these 
intravenous injections has been confirmed by Miiller, who also affirms that in septic 
diseases collargol may be given with as much trust as antitoxin in diphtheria. The 
value of the remedy is, however, very doubtful. The experiments of George Brunner 
have shown that collargol is precipitated by gelatin or bouillon; that it is not soluble 
in blood serum although it remains dissolved if the solution of it be mixed with the 
serum; that the germicidal properties of it are very feeble, — twelve hours' contact 
with the one-per-cent. solution of it being required to kill most pathogenetic bacteria; 
that when given subcutaneously or intravenously it has no apparent effect upon 
animals, and that granules of silver can be found later at the places of injection: 
finally, that whether given with infected matter or injected after the material, in 
the lower animals it has no influence over the processes of infection or upon the 
bactericidal power of the blood. The chills and other constitutional disturbances 
which were formerly produced by the intravenous injections of collargol were prob- 
ably due to the presence of impurities in the solutions used, and the whole drift of 
present evidence is to show, that collargol probably never circulates in the blood to 
any extent, and that it is physiologically inert. 

Argonin. Silver Caseinate. — An albuminous preparation of silver, readily 
soluble in warm or albuminous water, has been highly recommended in inflam- 
mations due to gonococci. Its ten-per-cent . solution is said to produce no pain; 
even in acute cases it may be used freely. 

Ichthargan. Silver-thio-sulphonate. — This compound of silver and ichthyol 
contains about thirty per cent, of silver and fifteen per cent, of sulphur. 
It is a brown amorphous powder, readily soluble in water, glycerin, and dilute 
alcohol, but insoluble in absolute alcohol; and is precipitated from its solution by 
sodium chloride and albumin; the latter precipitate, however, being redissolved 
by an excess of albumin. It is stated to add to its germicidal and antiphlogistic 
influences a distinct locally anesthetic power. 

According to the researches of Aufrecht, ichthargan is much more destructive 
to gonorrhceal, pyogenic, diphtheritic and typhoid germs than is either colloidal 
silver or protargol, its one-per-cent. ointment being as active as the fifteen-per- 
cent, of collargol. According to H. C. Wood, Jr., this preparation does not differ 
essentially in its physiological action from the ordinary salts of silver. Both Auf- 
recht and Wood, Jr., have found that ichthargan is much less toxic than silver 
nitrate. The experiments of Derby as well as of Aufrecht indicate that ichthargan 
is even more actively germicidal than silver nitrate. 

Ichthargan is being very largely used in gonococcal and other infective diseases 
of the mucous membranes; also in various infected ulcerations and skin diseases. 
It has been especially commended in various forms of rhinitis, tonsillitis, laryngitis, 
and other affections, chronic and acute, of the upper respiratory mucous membrane, 
either applied in spray of the glycerin solution varying from four to ten per cent., 
or less freely in solutions up to twenty per cent. The strength of the ichthargan 
solution varies in gonorrhoea from 1:500 to 1:3000 for injections; from 1:2000 to 
1:5000 for irrigation; one to three per cent, in instillations. In trachoma, gonor- 
rheal , and other infective conjunctivitis, the one- to three-per-cent. solution may 
be applied with a brush; 1:1000 used as a wash. In eczema, ulcerations, phleg- 
mons, vaginitis, and lymphangitis, the ointment, varying from one to fifteen per 
cent., is advised, well rubbed into the adjacent thoroughly cleansed healthy skin, 
and also applied directly to the affected surface if it be exposed. 



ASTRINGENTS 



321 



[ohthargan has also been administered Internally with asserted and excellent 
results for the relief of gastritis, and especially of gastric ulcers. Dose, one-twentieth 

to one-eighth Of a grain in half an ounce of water on an empty stomach. 

PftOT.vnnoL. — The chemical combination of silver and protein occurs as a fine, 
yellowish powder, readily Boluble in cold water. Its solution is precipitated by 
albumin, by dilute solutions of sodium chloride, or by dilute acids and alkalies. 
It is said to contain eight per cent, of metallic silver, and was originally proposed 
by Professor Niesser as having the antiseptic properties of the silver salts, and being 
able to penetrate tissues on account of its not coagulating albumin. According to 
the experiments of Petit jean, Athanasion, and Compareseo, the injection of prot ar- 
got into the jugular vein of t he dog produces in a very few minutes a fatal pulmonary 
oedema, probably due to deposition of silver and consequent mechanical obstruc- 
tion. Protargol has been much used in gonorrhoea, infective conjunctivitis of various 
forms, as well as in infected wounds. In gonorrhoea it may be used in strengths 
varying from one-half to two per cent., according to the mode of employment. 
In infected wounds a lengthened application of the five-per-cent. solution may be 
made, or the powder itself used by dusting, or a ten-per-cenf. ointment applied. 



REFERENCES. 



ASTRINGENTS. 



Heinz V. A. P. A., 1889, cxvi. 

Hosknstein Rossbach's Pharmakol. Un 

tersuch., Wiirzburg, ii. 



Orfila. 



ACETIC ACID. 

. . .Toxicologic, ii. 



TANNIC ACID. 

Daniels In. Dis., Bonn, 1864. 

Fikentscher In. Dis., Erlangen, 1877. 

Ki chhnmeister. . Arch. Phvsiol. Heilk., 1851, 

493. 

Lewin V. A. P. A., lxxxi. 74. 

Rosenheim B. K. W., xxxvi. 

Rosenstein Rossbach's Pharmakol. TJn- 

tersuch., Wiirzburg, 1875. 

Schreiber D. M. W., 1897. 

Schrofp; Clarus. .Husemann's Die Pflan- 

zenstoffe, 1005. 
Stockman B. M. J., Dec. 4, 1887. 

GALLIC ACID. 

S\c ( Chem. News, July, 24, 1871- 

AGARIC. 

Hofmeistek A. E. P. P., 1889. 

COTARNINE HYDROCHLORIDE. 

Mohr Ther. Geg., 1905, vii. 361. 



Kramolik . . . 



ALUM. 
.P. M. C. P., 1902, ii. 
LEAD. 



Annlschat A. E. P. P., x. 

Bardenhewer . . .B. K. W., 1877. 126. 

Birdsall N. Y. M. R., March, 1882. 

Buber Neurol. Centralb.. 1897, xvi. 

Chatin C. R. S. B., 1862. iv. 84. 

Claisse and Dupre ..La Presse Me'd., Paris, 

1897, iv. 

Crooke L. L., 1898, ii. 

Ccrci G. H. M. C, 1883, 552; Gaz. 

d. Ospitali, March, 1883. 
Df.bove and React Prog. M., 1876, 151. 
Degerine C. R. S. B.. 1880. 

21 



Lancereaux. 



Levy. 
Lbyden. . 



Dehoide and Leoomft. . L'Eclio Med. du Nonl. 

1898, ii. 
Ellenberger and Hofmeister. . Arch, f., 

Wissen. u. Prakt. Thier- 

heilk., x. 216. 

EuLENBERG D. A. K. M., iii. 506. 

Fisher A. J. M. S., 1892, civ. 

Freyer Z. Mb., 1881, i. 

Friedlaender . . . V. A. P. A., lxxv. 24. 

Frank D. A. K. M., xvi. 422. 

Geppert Z. K. M., v. 161. 

Gourbault Prog. M., 1880; A. de P., 

1873. 

Harnack A. E. P. P., 1878. 

Heubel Virchow and Hirsch's Jahr- 

biicher, 1871, i. 316. 
.Trans. Internat. Med. Con.. 

1881, ii. 191 ; Gaz. MeU 

Paris, 1862, 1871. 
S. Jb., clii. 250. 
.Z. K. M., 1884, 881. 

Lyon Gaz. des Hopitaux, 1889. 

Maier V. A. P. A., xc. 

Malassez A. de P., 1874, 50. 

Manouvriez L'Intoxication Saturnine, 

Paris, 1874. 

Melsens Ann. Phys. et Chim., xxv. 

Monakow Arch. f. Psychiat., x. 495. 

Moritz D. M. W., 1901, xvii., xviii. 

Oeller Festschrift d. Aerztl. Verein, 

Munchen, 1883. 
Oddo and Silbert. .Rev. de Me'd., Paris, 1892, 

xii. 

O'Carroll B. M. J.. 1893, i. 

Pagliano Marseille Me'd., 1891, xxviii. 

Pitt Trans. Path. Soc, London, 

1891, xlii. 

Popow V. A. P. A., xciii. 351. 

Potain La Semaine M^d., 1888. viii. 

Pouchet A. de P., 1879, xii, 74. 

Prevost and Binet. .R. M. S. R., 1889, ix. 

Putnam B. M. S. J., Feb. 1893. 

Putnam Trans. Amer. Neurol. Ass., 

1883 

Ransom B. M. J., 1900, i. 

Sabrazes and Bourret. . Cb. I. M., 1902. 

Sailer J. A. M. A., 1905, xliv. 1515. 

Schaffer Ungar. Arch. f. Med., 1893, 

xi. 
Schultze Arch. f. Psychiatr., 1885, 

xvi. 809. 
Stieglitz Arch. I. Psychiatrie, 1892 

xxiv. 
Valence Thesis, Nancv, 1888. 



322 



GENERAL REMEDIES 



REFERENCES (Continued). 



Von Wyss V. A. P. A., xcii. 

Vucetio Allgem. Wien. Med. Zeitung, 

1897, xlii. 
Vulpian Maladies du Syst. Nen-eux. 

1879. 

Wkstphal Arch. f. Psychiatr., iv. 776. 

Wood Therapeutics, i. 158. 

BISMUTH. 

Aemmer C. B. S. A. 1897 xxvii. 

Balzer C. R. S. B., 1889. 

Bennecke M. M. W., liii. 945. 

Bergeret and Mayencon . . J. A. P., 1873, 242. 
Dalche and Yillejean. .B. G. T., 1888, lvii. 
Feder-Meyer. . . . In. Dis., Wiirzburg, 1879. 

Haegler C. B. S. A.. 1895. 

Harnack Arzneimittellehre, 1883, 383. 

Heinz and Liebreich. .G. M. P., 1891. 
Kocher Volkmann's Klin. Vortrage 

No. 224. 

Laquer Ther. Geg., 1901. 

Mory In. Dis., Berne, 1883. 

Steinfeld A. E. P. P., xx. 41. 

Wood Trans. Amer. Neurolog. Ass., 

1883 23. 



Sacher 

ScHLOCKOXV . . 



ZINC. 

.Thesis, Dorpat, 1893. 
. D. M. W., 1879, 208. 

COPPER. 



Clapton M. T. G., .Tune, 1868. 

Coupin C. R. A. S., 1898, cxxvii. 400. 

Doty N. V. M. R., 1905, lxvii. E0. 

Dccom A. de P., 1877, iv. 183. 

Falck D. Kl., 1859. xi. 

Filehne D. M. W., 1893. xxi. 

Fowler Journ. Roy. Army Corp>, 

v. 391. 
Galippe Etude toxicol. sur la Cuiyre, 

Paris, 1875. 

Galippe C. R. A. S., lxxxiy. 718. 

Gildersleeve. . . . A. J. M. S., 1905, cxxix. 757. 

Kraemer A. J. Pharm., 1906, 140. 

Kurth N. Y. M. R., 1900 lviii. 



Lewin D. M. W., 1900. xxvi. 

Liegeois J. Pr., April. 1901. 

London Clinical Society . Transactions, 1870, 
13. 

Price N. V. M. K., 1903. 

SCHWABZ A. K. P. P., 1895. xxv. 

Stewart A. J. M. S., oxxix. 761. 

Von Bokay P. M. C. P., 1897, 33. 



aufrecht . . 
aufrecht. . . 
Bogolowsky 
bornemann. 
Brunner 



SILVER. 

. D. M. W., 1900, xx\i. 
. Merck's Annual Keport, 1902. 
.V. A. P. A., 1809, xlvi. 413. 
Ther. Geg., 1901. 
Fort. M., 1900, xviii. 
Chanevant and Robtbrnak. .0. It. S. B„ 

1903. Iv. 
Chariot and Bali. Gaz. Med., 1864. 

Crede A. K. C, 1897, Iv.j also 

1903, Lxix. 

Curci L. M. It., 1877, 72. 

Derby B. M. and S. J., cxlv. 34. 

Falk T. M . 1896, x. 

Frommann V. A. P. A., xvii. 135. 

Harnack Arzneimittellehre. 1883, 410 

Husemann . . Toxicologic Berlin, 1862, 
868. 

Krysinski L. M. R., Aug. 16, 1886. 

Lea Amer. Journ. Science, 1889, 

xxxvii. 479. 
Marshall and Nbavk B. M. J., 1906, ii. 359. 
MCller D. M. W., 1902. 



Ne I'M ANN. 

NlESSER 

ItlEMER 

ItOTJG ET 

RoZSAHEGZI. . 

Scattergood. 

Seiller 

Taylor 



Versmanns . . 
Wood, Jr. . . . 
Yandell 

ZWEIFEL 



. .Medizin. Jahrbuch., 1877. 
369. 

T. W., 1897. 

A. Ilk., x\i. 296; xvii. 330. 

A. de P.. 1873, 356. 
. A. E. P. P.. ix. 295. 
. .B. M. J., May, 1871. 
..J. A. M. S., i. 266. 
, .Med. Jurisprudence. 2d ed., 

i. 319. 
. V. A. P. A., 1859, xvii. 

X. Y. M. J.. April, 1903. 
. .Amer. Pract., June, 1872. 
. .Cb. G., 1900. 



FAMILY II.— TONICS. 



IRON. 

Iron is official in the U. S. Pharmacopoeia in a metallic state, as 
well as in a large number of salts. The salts may be conveniently di- 
vided into two groups, the soluble and the insoluble. The soluble salts 
of iron may be further divided into two groups, those in which the base 
is combined with an inorganic acid and those containing an organic 
acid radical. The latter class include the various citrates and 
tartrates and are frequently spoken of as the "scale salts" of iron 
from the fact that they occur in thin transparent scales, mostly of a 
garnet-red color — except the iron and quinine citrate, which is 
greenish-yellow. 

Official Preparations : (The important ones are marked with ]'■) 
The soluble solid preparations of iron are as follows: 

Ferri Chloridum (22 per cent.*) 1 grain (0.06 Gm.). 

t Ferri Phosphas Solubilis (12 per cent.) 5 grains (0.3 Gm.). 

Ferri Pyrophosphas Solubilis (10 per cent.). .5 grains (0.3 Gm.). 

Ferri Sulphas (20 per cent.) 2 grains (0.13 Gm.). 

Ferri Sulphas Exsiccatus 1 grain (0.06 Gm.). 

Ferri Sulphas Granulatus 2 grains (0.13 Gm.). 

Ferri et Ammonii Sulphas (11.5 per cent.). . .5 grains (0.3 Gm.). 

Ferri Citras (16 per cent.) 5 grains (0.3 Gm.)'. 

f Ferri et Ammonii Citras (16 per cent.) 5 grains (0.3 Gm.)'. 

Ferri et Ammonii Tartras (13 per cent.) •"> grains (0.3 Gm.)'. 

f Ferri et Potassii Tartras (15 per cent.) 5 grains (0.3 Gm.). 

Ferri et Quininte Citras (13.5 per cent.) 5 grains (0.3 Gm.)'. 

Ferri et Quinine Citras Solubilis (13.5 per 

cent.) 5 grains (0.3 Gm.). 

Ferri et Strychnine Citras (16 per cent.). . . .2 grains (0.13 Gm.). 

The insoluble solid preparations are: 

Ferrum (Iron Wire) Not used internally. 

t Ferrum Reductum (90 per cent.) 2 to 5 grains (0.13-0.3 Gm.). 

Ferri Carbonas Saccharatus 3 to 5 grains (0.2-0.3 Gm.). 

t Massa Ferri Carbonatis [Vallet's Mass] (20 

per cent.) 3 to 5 grains (0.2-0.3 Gm.). 

t Pilula? Ferri Carbonatis [Blaud's pills] 1 to 3 pills. 

Ferri Hypophosphis (22 per cent.) 3 grains (0.2 Gm.). 

Ferri Hydroxidum I to 1 ounce (15 to 30 Gm.). 

t Ferri Hydroxidum cum Magnesii Oxido \ to 4 fluidounces (15-120 C.c.). 

Pilulae Ferri Iodidi 2 pills. 

* The percentages given refer to the proportion of metallic irun present. 

323 



324 GENERAL REMEDIES 

The liquid preparations containing iron are: 

Liquor Ferri Chloridi (10 per cent.) 3 to 5 minims (0.2-0.3 C.c). 

tTinctura Ferri Chloridi (4.6 per cent.). ... 10 to 30 minims (0.0-2.0 C.c). 

t Liquor Ferri Subsulphatis (13.6 per cent.). 3 to 5 minims (0.2-0.3 C.c). 

Liquor Ferri Tersulphatis To make the Hydroxide. 

f Liquor Ferri et Ammonii Acctatis [Bash- 

am's Mixture] 4 fluidrachms (15 C.c). 

Glyceritum Ferri, Quininae et Strychninae 

Phosphatum 1.5 minims (1 C.c). 

Syrupus Ferri, Quininae, et Strychninae Phos- 
phatum 1 fluidrachm (4 C.c). 

f Elixir Ferri, Quininae et Strychninae Phos- 
phatum [Triple elixir] 1 fluidrachm (4 C.c). 

t Syrupus Ferri Iodidi 15 to 30 minims (1-2 C.c). 

f Mistura Ferri Composita [Griffith's mixture] \ to 1 fluidounce (15-30 C.c). 

Vinum Ferri 2 fluidrachms (8 C.c). 

Vinum Ferri Amarum 2 fluidrachms (8 C.c). 

Absorption. — Iron is a, constituent part of many tissues of (lie 
body, but is especially abundant in the red blood corpuscles. Ain<>n»; 
the older chemists Quevenne taught that the exhibition of the sails 
of iron had little influence upon the amount of iron in the urine. 
This fact was confirmed by Bunge and since then by numerous other 
chemists and gave rise to the belief by some that the ordinary salts 
of iron were not absorbed into the blood. This theory had at one 
time a large following and led to the manufacture of a large number 
of preparations in which iron was supposed to be present in the form 
more nearly resembling the combinations in which it was found nor- 
mally in the body, and which are generally known as "organic salts" 
of iron. In the light of more recent investigations, however, there 
appears no longer to be any room for doubt that the Pharmacopoeial 
salts of iron are absorbed from the intestinal tract, nor does there 
appear any good reason to believe that the so-called organic prepara- 
tions of iron have any advantage over the older combinations of 
this metal. 

The most important arguments which were advanced against the absorbability 
of inorganic iron through the intestinal tracts are: First, that the quantity of iron 
in the urine is not notably increased after the administration of iron by the mouth; 
second, that the amount of iron in the urine is increased after the hypodermic 
administration of iron; third, that the system requires extremely small quantities 
of iron, not over 10 milligrammes a day for the ordinary man. These facts have 
been so abundantly confirmed that they do not permit of contradiction, but, on the 
other hand, the conclusions drawn from them are not logically justified. 

To the first reason may be answered that absence of urinary elimination is not 
proof of non-absorption; it is perfectly conceivable that other organs, especially 
the intestinal tract, might eliminate the iron from the system, or that it might be 
stored up for considerable periods of time in the system. Experimentation has shown 
that this is the real explanation of the failure to find iron in the urine. Thus Gott- 
lieb obtained, after the hypodermic administration of iron, nearly ninety-seven 
per cent, of the injected iron from the feces, while Gottlieb, Jacobi, and Zaleski, 
all present evidence to show that iron is stored up in the liver. To the second argu- 
ment, while it is true that the quantity of iron in the urine is increased after the 
hypodermic administration, the amount which passes out through the kidney is 
much smaller than that which is eliminated by the intestinal tract. The third 



TONICS 355 

argument advanced against the absorption of iron presupposes thai the inorganic 

salts of iron act upon the system :is foods, which is probably tin! the case. 

On the other hand, there is to-day abundant evidence, of a direct nature, thai 

iron is absorbed from the intestinal tract. 

Kunkel for eight weeks fed tWO dogs upon milk, giving to one of I hem iron in 

addition, and bleeding each dog equally from time to time. Alter the killing of 
the dogs the blood and the various organs of the body were carefully analyzed, and 

it was found that iron was in distinct excess in all the organs of the dog to which 
the metal had been given, and that in the blood there was one and a half times as 
much of the iron, and in the liver eight times as much, as in the similar tissues or 
organs of the dog used for control, Justus Gaule detected chemically iron in the 
lymph coining from the thoracic duct of a rabbit into whose stomach a dilute solu- 
tion of the ferric chloride had been injected. Quincke not- only proved that iron is 
excreted from the mucous membrane of the large intestine, but also that absorbed 
iron can be detected in the walls of the duodenum, a fact which has been confirmed 
by Hall, by A. Hoffmann, and by Hare. Hall further discovered that if the feeding 
of a carnivorous animal with iron had been long continued, the metal could be 
detected in the pulp-eclls of the spleen and in the hepatic acini around the central 
vein. The conclusion of Hall, that iron occurs in the human system in two forms, 
one a fixed organic combination, — hemoglobin, — the other an inorganic or a very 
loose organic combination, is very plausible. According to Hall, it is the second 
combination whose amount in the system continually' varies with that of the iron 
taken into the alimentary canal. 

Physiological Action.* — It has been generally taught that 
iron acts in anemia by supplying a missing element necessary for 
the nutrition of the body, that is, as a food. But, while it is probably 
true that in cases of iron starvation the salts of this metal may be 
utilized as a food by the system, it is much more likely that in anemic 
conditions iron acts as a direct stimulant to the blood-making organs. 

To suppose that, because it is an essential constituent of hemoglobin, iron acts 
in the treatment of anemia as a food, is no more relevant than to claim that — 
because phosphorus is an essential constituent of the protoplasm, therefore, the 
administration of elementary phosphorus acts as a food; or to claim that — because 
strychnine is not a normal constituent of the protoplasm, therefore, it exercises no 
beneficial action upon the system. The fact that cases of chlorosis occur despite 
the daily ingestion of more than sufficient iron for the needs of the body, and that 
the administration of foods containing iron does not cure chlorosis, is very strong 
evidence that iron acts not as a food but as a direct stimulant influence upon the 
organs producing hemoglobin. f 

.Muller has found that in dogs rendered anemic by repeated bleeding and a 
diet as free as possible from iron the administration of an inorganic salt of iron 
increased the number of nucleated corpuscles in the blood. Moreover, Simon has 
shown that, not only is the hemoglobin increased by chlorosis, but also, that the 
blood globulins are augmented by iron. 

The question whether or not iron acts as a stimulant to the blood- 
making organs is closely connected with the question as to the effect 
of iron upon healthy individuals. It was formerly believed that the 

* V. H. Meyers and F. Williams (Arch. }. Exper. Path. u. Pharm., xiii. 76) have studied the 
effects of enormous doses of the iron and sodium tartrate upon the lower animals. Both frogs and 
mammals are killed by it, the symptoms in warm-blooded animals being vomiting, purging, great 
fall of the blood-pressure, muscular weakness, and finally coma and death. The experiments show 
that the heart is not much affected, but the vaso-motor system and the spinal motor centres are 
paralyzed. 

t The theory of Kletzinski, and of Bunge, that iron does good in chlorosis, by combining with 
hydrogen sulphide and thus preventing precipitation of food iron, has been shown to be false in 
both its pathology and its chemistry and has even been abandoned by Bunge himself. 



326 GENERAL REMEDIES 

proper administration of the metal to healthy man would produce 
an excess of the red blood-corpuscles, but more recent investiga- 
tions, while somewhat discordant and not conclusive, have unsettled 
this belief. 

The experiments of Nasse upon dogs are in favor of the older view, while (hose 
of E. C. Cutler and E. H. Bradford are in opposition to it. The first observer, giving 
iron with fat, noted that the specific gravity of the blood rose from 1052 to 1060.8, 
and the amount of the metal in the blood from 0.477 to 0.755 per thousand parts, 
both the result of increase in the corpuscular element. Cutler and Bradford experi- 
mented upon man, using the tubes of Malassez, the result being slight diminution 
of the red blood-disks. As, however, the experiments were only two in number, 
and the subjects not under complete control as to conditions of life, these 
observations can hardly be considered conclusive. 

It appears to be a well-established fact that one of the functions of the red 
blood-corpuscles is to convert oxygen into ozone, which is the efficient form of the 
element in the system (see A. Sasse). The iron oxide outside of the body certainly 
possesses an ozonizing power similar to that of the red disk. Thus, a spot of iron 
mould — i.e., iron oxide — on linen will in time destroy the fabric. The reason of 
this is the corroding action of the ozone which is slowly generated by the iron oxide. 
It would seem a -priori probable that, by increasing oxidation an increase of the 
iron in the blood should cause elevation of temperature and increased elimination 
of urea. The studies of W. Pokrowsky have shown that, in cases of anemia, after 
the exhibition of iron the temperature does rise, even when in the beginning it 
was not below normal, and that simultaneously there is an increase in the daily 
elimination of urea; and the experiments of Botkin, as quoted by Sasse (we have 
not seen the original), establish the same fact in regard to healthy men. The in- 
creased oxidation cannot be due simply to an increase in the number of the red 
corpuscles, for while the latter accrue slowly, Pokrowsky found that the tempera- 
ture sometimes rose within five hours after the exhibition of the first dose. 

Therapeutics. — Leaving out of consideration those cases 
which may be spoken of as instances of "accidental anemia, " — i.e., 
anemia due to hemorrhage, poison, starvation, or other temporary 
cause, which has passed off or is removable, and in which iron may 
be given as an aid to the rebuilding of the blood, — we find that prac- 
tically the anemias are divided into two sets: those in which there 
is a pronounced lessening in the percentage of hemoglobin in the 
blood but not a corresponding lessening in the number of red blood- 
corpuscles, and those in which the red blood-corpuscles are greatly 
diminished in number. The first class of cases is typified in chlorosis, 
the second in pernicious anemia. 

Of the value of iron in chlorosis there can be no doubt. Thus, 
Simon reports a case of chlorosis in which, under the steady use of 
iron for sixty-four days, the globulin increased from 30.86 parts to 
90.80 parts per thousand, and the hemoglobin from 1.431 parts to 
4.598 parts per thousand; and Cutler and Bradford have obtained 
confirmatory results with Malassez's tubes. In most cases of essential 
anemia with great lessening in the number of red blood-corpuscles, 
typified by leukemia and pernicious anemia, iron is of no service 
whatever. Unfortunately, the line between the two sets of cases of 
anemia is in nature not so sharp as it can be made in treatises, and 
we have seen cases presenting a chlorotic form of anemia, in which 



TONUS 327 

the anemia failed to be affected at all by iron or any other treat- 
ment, remaining almost as persistent and unconquerable as the 
blood-lesion of leucocyt hernia. 

Almost all the preparations of iron are more or less astringent, 
and when in the blood very probably exert a direct influence upon the 
tissues, contracting them not merely by increasing their tone, but 
also by acting on their vital contractility. 

Administration. — When iron is used as a hematinic a preparation 
should be chosen which has little astringency. Among the most use- 
ful for adminisl ration in pill form are the mass of ferrous carbonate and 
the reduced iron, while, if a soluble preparation is desired, either the 
soluble phosphate or the iron and ammonium tartrate may be chosen.* 

Spurred on by the theory that the inorganic preparations of iron are not ab- 
sorbed, pharmaceutical chemists have put forth many organic preparations. Of 
this multitude only one deserves any mention and that is the one commended by 
Sthnuedeberg and Marfori, under the name of ferratin, a proteid compound con- 
taining from four to eight, per cent, of iron, which is affirmed to be the form in which 
iron exists in the liver, and out of which in the body the hemoglobin is directly made. 
There is, however, neither clinical nor experimental evidence indicating that ferra- 
t in is superior to the older compounds. Hochhaus and Quincke found that ferratin 
and the older compounds could be traced through the duodenum into the mesen- 
teric glands with equal facility; and in an elaborate study on the absorption and 
elimination of the iron, Cloetta was unable to perceive any difference between organic 
and inorganic preparations of iron in relation to their building up of the blood. 

There are persons in whom iron produces headache: this can in 
some cases be obviated by the use of laxatives. The observations of 
M. Petit, N. A. Bubnow, etc., that the iron preparations in large doses 
inhibit the digestive processes, throw some light upon these cases. 
Our experience is that gouty or rheumatic patients bear iron badly, 
and that sometimes its exhibition seems to aggravate the arthritic 
symptoms. The chief contraindication for the use of iron is the exist- 
ence of plethora or of catarrhal disease of the gastro-intestinal tract. 

The peculiar actions of certain salts of iron will be considered 
under their respective preparations. 

All of the salts of iron have chalybeate properties, although, in 
the case of some of the preparations, their other effects entirely 
outweigh their virtues as hematinics. The most notable of these 
preparations are as follows: 

Solution of Ferric Substjlphate, Monsel's solution, is actively 
astringent and is used chiefly as a styptic for the control of local 
hemorrhages. It may also be used with advantage in the treatment 
of hernatemesis in doses of from one to five minims, well diluted, 
given as often as necessary. In overdose Monsel's solution acts as 
an irritant poison. The chemical antidote should be an alkali in the 
form of soap or washing soda. Sulphate of iron is also astringent 
but is much more irritant and comparatively rarely employed. 

* The alkaloidal compounds with iron are very ineligible preparations, because they do not 
allow the practitioner to vary the proportionate doses of the two ingredients. 



328 GENERAL REMEDIES 

Tincture of Chloride of Iron, although widely used as a chalyb- 
eate, is, on. account of its astringent properties, much more likely 
to produce gastro-intestinal disturbances than many other salts of 
iron. It, however, appears to possess certain peculiar properties 
which make it valuable. Decidedly diuretic and escaping through 
the kidneys, it directly affects the genito-urinary mucous membrane. 
It is much used in chronic Bright's disease and combined with tinc- 
ture of cantharides in gleet. In erysipelas it is constantly employed 
with remarkable results, controlling the disease in a manner not yet 
understood. Analogy has suggested its employment in other ady- 
namic affections, such as diphtheria and pyemia, but its value in these 
diseases is much more doubtful. It is so destructive to the teeth 
that except in the toothless its use as a gargle is unjustifiable; and 
even in its ordinary therapeutic use, by the employment of a tube, 
etc., the teeth should be protected as far as possible. 

Syrup of Ferrous Iodide combines the alterative effects of iodine 
with the tonic action of iron and is largely used in the treatment of 
scrofula. It has, however, no advantage and several disadvantages 
over the extemporaneous combination of an iodide with an iron salt. 

Ferric Hydroxide, also known as sesquioxide of iron and the 
hydrated oxide of iron, is used chiefly as an antidote to arsenic. It is 
formed when an alkali is added to a solution of an iron salt. In 
emergency any alkali and a soluble iron salt may be used to make the 
antidote, but ferri hydroxidum cum magnesii oxido, of the U. S. Phar- 
macopoeia, which is made by adding an excess of magnesium oxide 
to a solution of ferric sulphate, has the advantages that the magnesia 
is non-irritant and is itself somewhat antidotal to arsenic. As the 
ferric hydrate is perfectly innocuous, and especially since it acts only 
when in excess, it should be very freely administered. A tumbler- 
ful of the ferric hydroxide with magnesia may be taken at once and 
repeated several times if necessary. 

For antidotal purposes ferric hydroxide should be freshly prepared, and should 
be so moist as to constitute a magma. Its virtues are deteriorated by age, even when 
it is kept under water, and are entirely destroyed by drying. If the solution of the 
ferric sulphate be not at hand in an emergency, the chloride will yield just as useful 
a product, and sodium carbonate or, better still, magnesium carbonate, may be 
substituted, if circumstances necessitate it, for the ammonia. The precipitate falls 
at once, and may be washed by putting it in a piece of muslin, squeezing out the 
original fluid, and then pouring on some fresh water. Of the precipitated ferric 
hydroxide a tablespoonful may be given at a dose. 

Manganese. — The salts of Manganese have been supposed to 
possess therapeutic properties similar to those of iron. The metal 
manganese certainly exists in the blood, but its salts have failed to 
gain the confidence of the profession, although highly recommended 
by Harmon, of Belgium, and by Petrequin as an adjuvant to the 
chalybeates. In Garrod's experiments upon anemia the preparations 



TONICS 329 

of manganese failed to be of service. According to C. C. Gmelin, 
the sulphate acts as a powerful cholagogue on the lower animals, 
and Thomson states that it is a purgative to man in doses of one or 
two drachms. Leand affirms that the manganese oxide is thera- 
peutically equivalent to the preparations of bismuth excepting in 
that it does not constipate, and that it may be used with advantage 
in gastralgia, pyrosis, and similar stomachic derangements. 

Official Preparations : 

Mangani Dioxidum Prsecipitatum 5 to 10 grains (0.3-0. (> dm.). 

Mangani Hypophosphis 5 to 10 grains (0.3-0.6 Gm.). 

Mangani Sulphas 5 to 10 grains (0.3-0.6 Gm.). 

MINERAL ACIDS. 

Sulphuric, hydrochloric, nitric, and nitrohydrochloric acids, 
when in concentrated form, rapidly destroy all organic tissues, and 
are, therefore, corrosives, hydrochloric acid being the feeblest. 

Owing to its abstraction of the element of water from the carbon 
of organic tissues, sulphuric acid blackens organic matter at the 
same time that it destroys its texture; nitric acid stains organic tissue 
a deep yellow color; nitrohydrochloric acid produces a somewhat 
similar but much less pronounced discoloration. In the detection 
of poisoning by one of these agents the color of the stain upon the 
person or clothing is often of great assistance. Holes made in the 
linen by one of these acids are to be distinguished from those made 
by fire or mechanical violence by the pulpy character and acid reaction 
of the edges. 

The general symptoms of poisoning by mineral acids are similar, 
and depend for their severity especially upon the amount and the 
concentration of the dose taken, although sulphuric and nitric acids 
are more powerful than is hydrochloric acid.* Death from collapse 
has resulted in two and a half hours, but months may be required in 
the working out of the fatal result. The symptoms are immediate 
pain in the mouth, gullet, and epigastrium, violent vomiting (after 
sulphuric acid the matters may be tarry), and rapid collapse marked 
by cold wet surface, feeble pulse, and suppressed voice. The mind 
is usually clear until very late in the poisoning. 

After a small dose the chief symptoms may be connected with 
the upper digestive passages. Thus, Maukopff has recorded sup- 
purative parotitis largely due to the closure of the duct of Steno. 
Ulceration of the larynx or oesophagus has frequently been noted. 
Desquamative nephritis may be developed several days after sub- 
sidence of the first symptoms. In a case of sulphuric-acid-poisoning 
recorded by Maukopff, the urine which had ceased to be albuminous 
on the third day became so again on the twentieth, with a simul- 
taneous development of casts containing blood-corpuscles; after 

* Cases of sulphuric-aei.l-pnisoniiig (Med. Times und Gti:., 18(>3, i.). 



330 GENERAL REMEDIES 

death tubular nephritis was found. Another symptom noted by 
Maukopff was intercostal neuralgia. 

After death, destruction of the oesophagus, stomach, or air- 
passages is usually found, the color of the slough — black after sul- 
phuric, yellow after nitric acid — being characteristic. Probably in 
all cases in which death does not take place too early, wide-spread 
degeneration of protoplasm takes place. A. D. Kazowsky has found 
that this involves the cells of the heart-ganglia, which undergo 
parenchymatous swelling, followed by necrosis of the cells and vacu- 
olization not only of the nuclei but also of the general protoplasm. 

When the dose has not been sufficient to kill, protracted illness 
from local organic alterations usually results. 

The treatment of a case of acid-poisoning consists in the imme- 
diate administration of soap, chalk, whitewash, magnesia, or other 
available antidote. Notwithstanding Christison's condemnation of 
the alkaline carbonates as too irritating, they should be used 
unhesitatingly in dilute form if immediately at hand. 

Sulphuric Acid. — Oil of Vitriol is, when pure, a colorless, heavy 
liquid which on exposure to the air rapidly absorbs moisture. The 
official acid has a sp. gr. of 1.826. 

Official Preparations: 

Acidum Sulphuricum Not used internally. 

Acidum Sulphuricum Dilutum (10 per cent.). 15 to 30 minims (1-2 C.c). 
Acidum Sulphuricum Aromaticum (20 per 

cent.) 15 to 30 minims (1-2 C.c). 

Concentrated sulphuric acid is not rarely used as an escharotic, 
for which purpose it is mixed with finely powdered charcoal so as 
to form a paste. Appropriately diluted, it has been employed as a 
stimulant and astringent lotion in venereal and other indolent ulcers. 
Internally, sulphuric acid is very useful as an astringent in colliqua- 
tive sweats (night-sweats) and in profuse serous diarrhaas. We have 
used it with great advantage in the sudden serous vomiting and 
purging of infants known as cholera infantum. 

It has been employed with advantage in cholera, and a remarkable 
series of observations by R. G. Curtin at least furnish good reason 
for further testing its powers as a prophylactic against this disease.* 

The facts recorded by Curtin are as follows. A very severe epidemic of the 
disease ceased in the Insane Department of the Philadelphia Almshouse within 
twelve hours after the lunatics were all put upon the free use of sulphuric- acid 
lemonade, the only new case after this being in a man who refused to use the prophy- 
lactic. Two days after the use of the sulphuric acid was stopped two new cases 
occurred, and the epidemic was again arrested by the use of the acid. In the sur- 
gical wards of the Hospital Department the acid was used from the beginning of 
the epidemic; and these wards, although in no way isolated, were the only parts 
of the institution unvisited by the disease. The sulphuric acid probably acted by 

* It is very probable that other acids are equally antidotal to the cholera germ, since Richard 
P. Strong found that the addition of one per cent, of citric acid to water infected with the cholem 
germ made it safe to drink. — Report Government Laboratories, Philippine Islands, Sept. 1, 1903. 



TONICS 331 

producing an exoessive acidity of the alimentary canal, it being well assured that, 
iho cholera organism will develop only in an alkaline condition <>f the alimentary 
tract. Thus, the dog, whose digestive tract is highly acid, resists the action of the 

bacillus unless an alkaline carbonate be freely given, when choleraic symptoms 
appear after the administration of the cholera organism. 

Sulphuric acid was formerly used in hemorrhages, but is now rarely 
employed. It is, we think, much less efficacious than are some other 
remedies. In acute lead-poisoning the dilute acid is an efficient anti- 
dote, and in white lead works the free use of sulphuric acid lemonade 
by the employees is said to be advantageous as a prophylactic against 
the chronic poisoning. 

Administration. — Sulphuric acid should be given properly 
diluted, and with the requisite precautions to prevent its injuring 
the teeth. 

Hydrochloric Acid is a colorless aqueous solution of hydrochloric 
acid gas, having the specific gravity of 1.158 and containing 31.9 
per cent., by weight, of the gas. The yellowish tint of commercial 
hydrochloric acid is due to the presence of ferric chloride, or organic 
matter. 

Official Preparations: 

Acidum Hydrochloricum (32 per cent.) Not used internally. 

Aciduin Hydrochloricum Dilutum (10 per 

cent.) 1.5 to 60 minims (1-4 C.c). 

Hydrochlo.'-ic acid, being the normal digestive acid of the stomach, 
is often advantageous in cases in which chronic indigestion is connected 
with the failure to secrete acid in the stomach, and the combination 
of it with strychnine, bitter tonics, and aromatics is often serviceable. 
In the so-called " Swedish plan" of treatment of typhoid fever, hydro- 
chloric or other mineral acid is given in very large quantities. 
Although the method was at one time much in vogue, it has no 
justification in results, and is to be avoided. The local use of hydro- 
chloric acid in diphtheria, made famous by Bretonneau, has deservedly 
gone into oblivion. As a poison, hydrochloric acid is the most 
feeble of its class, recovery having occurred after the ingestion of 
an ounce. 

Nitric Acid is a liquid of the specific gravity of about 1.403, 
which as first made is colorless, but by exposure to the light acquires 
a yellow tint. It oxidizes all the common metals except gold, and is 
exceedingly corrosive to living tissue, which it stains an indelible 
yellow. When diluted it converts most animal and vegetable 
substances into oxalic, malic, or carbonic acid. 

Official Preparations : 

Acidum Nitricum (68 per cent.) Not used internally. 

Acidum Nitricum Dilutum (10 per cent.) 15 to 60 minims (1-4 C.c.). 



332 GENERAL REMEDIES 

When taken internally in small amount, nitric acid acts as a stimu- 
lant upon the glandular system of the alimentary canal, and in serous 
diarrhoea appears to exert an astringent influence. 

Nitric acid is frequently used as a powerful escharotic in cases 
of chancre, venereal or other warts, hospital and other acute gangrenes. 
In many instances in which formerly it was relied upon it has been 
replaced by antiseptic measures. 

In its employment care should be taken to protect the sound tissue by oil or, 
still better, by a layer of soap. It may be applied by means of a splinter of wood, 
or, if it is to be used more freely, by a little mop. When it lias penetrated as deeply 
as is desirable, washing the part with warm soapsuds will prevent further action. 

Internally, nitric acid has been used in low fevers, but with very 
doubtful advantage. In dyspepsia, in chronic hepatic congestion, in 
the oxalic acid diathesis, and in the dyscrasia of constitutional syphilis 
nitric acid has been employed with advantage, but is much inferior 
to nitrohydrochloric acid. 

In 1826 Hope asserted that Nitrous Acid has a specific action in 
serous diarrhoea, including the sudden acute diarrhoeas of hot climates, 
and in the chronic dysenteries originating under similar circumstances. 
The formula he employed is as follows: R Acidi nitrosi, f.^i; Misturae 
camphorae, fgviii; Misce, et adde Tinct. opii, gtt. xl. S. — A fourth 
part to be taken every three or four hours. 

Under the name of Hope's Camphor Mixture a preparation similar to this has 
been much used (Mislura Camphoro? Adda, N. F.) but has gradually lost the con- 
fidence of the profession, chiefly, we believe, because on theoretical grounds the 
original formula has been departed from. The Nitrous Acid of the shops is an 
orange-red liquid, which may be looked upon as a solution of nitric oxide in nitric 
acid. When it is diluted with water it is after a short time converted into simple 
nitric acid. For this reason it has been customary to substitute nitric acid for the 
Nitrous Acid of Hope's original formula. It should be noted, however, that the 
latter provided only sufficient of the remedy to last a few hours, and, as the reaction 
which has been spoken of requires some time for its performance, we do not think 
that theory in truth warrants the change. Practically we have failed with the 
new formula, when immediate relief was afterwards obtained by the use of the 
medicine prepared according to the old plan. Made in this way and used while 
fresh, Hope's Camphor Mixture is a veiy efficient though disagreeable remedy in 
serous diarrhoeas connected with disordered secretion of the liver and other glands 
of the alimentary canal. 

Nitrohydrochloric Acid is made by mixing nine parts of nitric 
acid with forty-one parts of hydrochloric acid. If the acid be 
sufficiently strong, an orange-colored liquid will be formed with the 
evolution of intensely irritating vapors. 

After standing for a length of time, the red color of freshly mixed nitrohydro- 
chloric acid changes to a golden yellow. It is in this state that the U. S. Pharma- 
copoeia directs the acid to be used. By longer standing the golden yellow becomes 
lemon yellow, and the odor of chlorine is almost entirely lost. These changes are 
hastened by light, but will occur in the dark and in well-stopped bottles. Although 
the golden-yellow acid is directed by the Pharmacopoeia, yet careful clinical studies 
have convinced us that the acid acts much more efficiently when freshly prepared 



TONICS :;:;:; 

:uul of a deep red color. In some cases it lias seemed to U8 useful only when in 

the latter form. The lemon yellow acid is comparatively inactive. 

Official Preparations : 

Acidum Nitrohydrochloriourn 3 to 8 minims (0.2-0.5 C.c.). 

Aeitlum Nitrohydrochloricum Dilutum IS to •!() minims (1—2 C.c). 

The remedial value of nitrohydrochloric acid depends chiefly 
upon the power which it possesses to a much greater degree than any 
Other of the mineral acids of influencing the action of the liver and 
other glandular organs of the alimentary canal. Originally proposed 
by Scott, of Bombay, in the chronic hepatitis of hot climates, it has 
been used with great success by Annesley, Martin, and other famous 
India surgeons. The remedy would seem not to be indicated in 
hepatitis with high fever and a tendency to rapid suppuration so 
much as in the slower form of the affection, which normally ends in 
chronic enlargement and induration of the viscus. Both in the 
habitual congestion of the liver and in the milder affection known as 
biliousness, whose pathology is probably a torpid condition of the 
small glands of the alimentary mucous membrane as well as of the 
liver, nitrohydrochloric acid has yielded in our hands most excellent 
results. That the remedy does act upon the liver is proved by the 
fact that in these cases it sometimes produces violent bilious diar- 
rhoea. When jaundice depends upon obstruction or upon any of the 
severer organic diseases of the liver, the acid is of little if any use; 
when, however, the jaundice depends upon torpor of the liver, or 
even when it is catarrhal in origin, the remedy may be of great service. 
Even in the early stages of cirrhosis, while the liver is still enlarged, 
nitrohydrochloric acid should be tried, as in some cases apparently 
of this character great benefit has been derived from its use. 

In those forms of chronic diarrhoea in which the disease is really 
an intestinal dyspepsia, nitrohydrochloric acid may be of great ser- 
vice. As the effect of the acid is not a sudden one, it is evident that 
it acts in these cases not as an astringent, but by restoring the normal 
digestive power. 

There is a morbid condition, oxaluria, probably dependent upon 
defective primary assimilation, in which the chief symptoms are 
general malaise, a feeling of weakness, a lack of elasticity, and a very 
great depression of spirits, with the crystals of calcium oxalate 
generally present in the urine, and in which nitrohydrochloric acid 
produces in a few days a surprising revolution. 

As a "blood-purifier" the acid has been employed in constitutional 
syphilis and in various ulcerative skin affections. In these diseases 
it no doubt does good by improving digestion and increasing glandular 
action, but there is no reason to believe that it is a direct alterative. 

Administration. — For reasons which have already been given, 
when nitrohydrochloric acid is administered internally it should be 
freshly prepared; and, as the changes which have been spoken of 
take place more rapidly when the acid is mixed with water, the 



334 GENERAL REMEDIES 

diluted nitrohydrochloric acid is an ineligible preparation. As light 
hastens its deterioration, the acid should always be kept in a dark 
bottle with a glass stopper. Directly after mixing the acids the 
evolution of gas may be so great as to necessitate its being allowed 
to escape. After six or eight hours, however, the bottle should be 
closely stopped. The acid should be properly diluted, and taken 
through a tube after meals. 

In chronic hepatic diseases the external application of the acid 
appears to give even better results than its internal use. In India, 
according to Sir Ronald Martin, the bath is used as follows: 

Take Hydrochloric acid f J iii, Nitric acid f J ii, Water f ^ v. Mix. Two gallons 
of water and six fluidounces of the above mixture suffice for a bath, which will keep 
fit for use during three days, provided half a fluidounce of acid and a pint of water 
are added morning and evening. The bath must of course be given in wooden or 
earthenware vessels, and if it becomes necessary to warm it only a portion should 
be heated and the rest then added. In urgent cases the whole body may be im- 
mersed in the bath; but generally a foot-bath is preferable, the inside of the thighs 
and arms and the hepatic region being at the same time sponged. The bath should 
be repeated twice daily, lasting each time for ten or fifteen minutes. 

We have had no experience in this method of using nitrohydro- 
chloric acid, but have derived great benefit from the application of 
the acid over the hepatic region. 

A large piece (eight by ten inches) of spongio-piline, or of canton flannel (several 
layers), should be wrung out in a lotion of a strength varying, according to the 
irritability of the patient's skin, from one to three fluidrachms to the pint, and 
applied over the right hypochondrium, and covered with a piece of oiled silk sup- 
ported by a bandage. The application sometimes causes a prickling sensation, and 
after a time may produce a profuse local sweating. The dressing may be left on 
from half an hour to an hour, and be repeated three or four times a day: some 
patients can wear it almost continuously. 

Phosphoric Acid — Orthophosphoric acid (H 3 P0 4 ) results from 
the burning of phosphorus in the air, but is prepared commercially 
by the action of sulphuric acid upon bone-ash, which consists chiefly 
of calcium phosphate. The official acid contains eighty-five per cent, 
of the tribasic acid of chemists.* It is a colorless, inodorous, sour 
liquid, of a syrupy consistence, which has a very acid reaction, and 
is corrosive to animal tissues. 

Therapeutics. — Phosphoric acid has been used considerably as 
a tonic and alterative, especially in scrofulous diseases, but seems to 
have no other value than that of a very feeble and doubtful stimulant 
to the digestive apparatus 

Official Preparations : 

Acidum Phosphoricum 5 to 10 minims (0.3-0.6 Gra.). 

Acidum Phosphoricum Dilutum (10 per 

cent.) i to 1 fiuidrachm (2-4 C.c). 

Sodii Phosphas f 30 grains (2 Gm.). 

Calcii Phosphas Pnecipitatus 15 grains (1 Gm.). 

* It has been affirmed that the bibnsic pyrnphosphoric acid is a cardiac sedative 'see Jnurn. nj 
A net. mid Physiol., xi.). 

t For description of sodium phosphate as :i cathartic see p. 50S. 



TOXICS 335 

CALCIUM PHOSPHATE. Precipitated Calcium Phosphate is a 
white, inodorous, tasteless powder, almost insoluble in water or 
alcohol but soluble in dilute acids. Calcium phosphate is an abun- 
dant ingredient of bone, but also exists in notable quantities in all 
the tissues, ami is probably as essential to their health as to that of 
bone. Whenever it is taken out of the food of animals, although 
they be otherwise well fed, sooner or later they waste, sicken, and die. 

Chossat fed pigeons exclusively on corn containing very little of the calcium 
phosphate, and found that after some months they wasted, were affected with 
diarrhoea, and died. According to lloloff, a herd of cows which had been fed upon 
hay from a certain meadow were very much out of health, and suffered from frayil- 
itas ostium. On examination, the hay was found to be nearly free from earthy 
salts, and upon bone-meal being given to the cows they recovered their health in 
four weeks. The same authority further states that in some meadows with which 
he is acquainted the disease is endemic among the cows because the grass is so poor 
in phosphates. Haubner also affirms that cattle fed exclusively upon potatoes, or 
upon roots very poor in phosphates, fail to fatten, become weak, and are likely to 
suffer from caries, but that if the calcium phosphate be given they rapidly improve; 
and E. Yoit states that rachitis without emaciation can be produced in three or four 
weeks in young dogs by taking the calcium phosphate out of the food. 

Hegar has considered the absorption of the calcium phosphate, 
when given as a medicine, very doubtful, because when he exhibited 
it freely there was no increase in the amount of the phosphoric acid 
or of the earthy bases in the urine. Boker, on the other hand, has 
found that if the drug be given to those wet-nurses whose milk con- 
tains an abnormally small amount of phosphates, the milk soon 
becomes rich in the earthy salts, and L. Perl has found that adminis- 
tration of the phosphates is followed by an increase in their amount 
in the urine. Further, Albert Riesell has shown that the phosphates 
are eliminated by the intestines, and therefore that even if it were 
a fact that their renal excretion is not augmented by their adminis- 
tration, it would not prove that they are not absorbed. Teissier 
has found that in the early stages of phthisis there is a very great 
increase in the excretion of the earthy phosphates by the kidney, 
and the researches of Beneke* are said to have shown that this 
increased renal elimination, which plainly occurs in several allied 
diseases, is not accompanied by any increase in the amount ingested 
in the food or decrease of the amount eliminated by the intestines, 
and that, consequently, there is a very decided wasting of the normal 
phosphates of the body. This being so, the use of phosphates in these 
diseases is as rational as that of iron in anemia. 

Therapeutics. — According to Dusart, to Beneke, and to 
Teissier, the diseases in which the calcium phosphate is especially 
indicated are rachitis, osteomalacia, phthisis, and scrofulosis. It is 
evident that the indications for the earthy salts are very strong in 
the first two of these affections, and clinical experience has certainly 

* We have not had access to the original memoir of Beneke (Zur Wiirdigung lies Phosphors, 
finikin in phyaiolog. und therapeut. Beziehung, Marburg, L870). See Schmidt's Jahrb., cli. 138, 



330 GENERAL REMEDIES 

borne out the results of a priori reasoning. In scrofidosis the call for 
the drug is not so plain; but Beneke states that in many cases, if 
the urine be examined, it will be found to be abnormally rich in earthy 
phosphates, and that under these circumstances the remedy is of 
the greatest value. Cases are not rare of children of slow develop- 
ment, often seemingly well nourished and robust, and yet really pale 
and with flabby flesh, but without any distinct symptoms or marks 
of scrofulosis or of rachitis. Under these circumstances, the child 
is in a condition allied to that of the diathesis spoken of, and calcium 
phosphate is serviceable. In cases of delayed union after fracture 
the present remedy is seemingly indicated, especially since Dusart 
has experimentally proved that when given to animals whose bones 
have been broken it hastens union and makes the callus abnormally 
heavy and firm. Calcium phosphate has been recommended in vari- 
ous diseases other than those mentioned, but its value in them is 
much more doubtful. Bennett commends it in chronic phthisis; 
Piorry, in syphilitic periostitis; Beneke, in syphilitic gummqta; Scho- 
nian, and also Kugelmann, in the menorrhagia of anemic women. 
Beneke calls attention to the use of it during pregnancy, and believes 
that it exerts an influence on the foetus, so that women who have 
borne only rachitic children will bring forth healthy offspring. 

Administration. — Calcium phosphate is usually administered 
dissolved by means of lactic acid in conjunction with cod-liver oil, 
especially as the so-called emulsion of cod-liver oil and lactophosphate 
of lime, which, Avhen properly prepared, contains fifty per cent, of 
cod-liver oil and two grains of the calcium phosphate to the drachm. 
Dose, one to four teaspoonfuls. 

Hypophosphorotjs Acid is never used internal!}' in a pure con- 
dition, but various combinations of it with mineral bases and alka- 
loids have been largely used as tonics and reconstructives in the 
debility of phthisis, neurasthenia, and allied conditions. In our experi- 
ence these combinations have seemed to exert no other influence in 
disease than that of their active bases. According to the researches 
of Paquelin and Joly and of A. Boddaert, the hypophosphites are 
rapidly eliminated through the kidneys in an unchanged condition. 
Boddaert affirms, on what we believe to be insufficient evidence, 
that they increase distinctly the elimination of urea, of phosphorus, 
and of chlorine. 

Official Preparations : 

Acidum Hypophosphorosum (30 per cent.). . .Not used internally. 
Acidum Hypophosphorosum Dilutum (10 

per cent.) 8 to 15 minims (0.5-1 C.c). 

Calcii Hypophosphis 15 grains (1 Gm.). 

Ferri Hypophosphis 8 grains (0.5 Gm.). 

Potassii Hypophosphis 15 grains (1 Gm.). 

Sodii Hypophosphis 15 grains (1 Gm.). 

Syrupus Hypophosphitum 1 to 2 fluidrachms (4-8 C.c). 

Syrupus Hypophosphitum Compositus 1 to 2 fluidrachms (4-S C.c). 



TONICS 337 

Gi.ycero-Phosphoric Acid. — As is well known, the nervous 
tissues of the body contain a notable percentage of phosphorus. It 
is present in the form of glycero-phosphoric acid. This fact has led 
to its employment as a nerve tonic in such conditions as neurasthenia, 
locomotor ataxia, and pkosphoturia, with results asserted to exceed 
those obtained from phosphorus in any other form. It is given either 
in the form of the acid itself or of sodium or calcium glycero-phosphate 
in doses of two *o five grains (0.1-0.3 Gm.). 



REFERENCES. 

IRON. Basse Vierteljahr. f. Prak. Heilk., 

!"■** S. Jb., oaxxxvi. Schmibdkberg and Mari-ori. .A. E. P. P., 

BOBNOW Z. P. C, VII. xxix xxx jjj 

r, " ,VTA *\«i P - P - 1897 ' iKJCViii. SlMON Animal' Chemistry, London, 

184 1 ) 

i;, i , , .< and Hh.u.koui. A. .1 M S., 1878, 78. SocIN Z. P. 0., 1890-91. 

liU II-; 1J. ftl. V\ ,, 1NH), XXII. >/ Vf , K1 a tt> t> p -.,,::; 

llu, \. A. P.. IS90. /ialeski A. L. I. 1., xxm. 

IUmiu hc.kk Z. P. C. 1879, ii. 

Hare Arch. f. Verdauungs Krank., 

1898. Garrod M. T. G., 1863. 

Hochhaus and Quincke. .A. E. P. P., 1896, Leand Gl. M. J., Jan. 1805. 

xxxvii. 159. Pf.trequin Nouvelles Recherches du 

Hoffmann V. A. P. A., 1895, cli. Manganese, Paris, 1852; 

Jacobi A. E. P. P., xxviii. 3. B. G. T., March, 1852. 

Kinkf.i. A. G. P., lxi. 

MoF.RNKi! S. .lb., cexxxix. 227. MINERAL ACIDS. 

M0M.BR V. A. P. A 1901 1 104, 430. Curtin P. M. T., iii. 049. 

Nassk L. M. R., 1877, 498. Kazowsky Centralb. f. AUk. Path. u. 

Pokrowsky \ . A. P. A., xxu. Path. Anat., 1894, v. 

Quincke A. E. P. P., 1896, xxxvii. Preyer C. M. W., 1875, 578. 



MANGANESE. 



FAMILY III.— ALTERATIVES. 



There are employed by practitioners of medicine, to affect cer- 
tain diseases most intimately connected with the processes of nutri- 
tion, various substances which do not, at least in the doses commonly 
used, produce any very obvious symptoms. It is to medicines of this 
character that the name of Alteratives has been applied, because when 
administered they seem simply to alter morbid processes. 

Speculation has been rife as to the mode in which alteratives influence the 
body; and as the accepted pathology has been humoralistic or otherwise, so has it 
been strenuously argued that they act upon the vital fluid, or upon the solids of the 
body. The term "purifying of the blood" has been especially applied to their 
action, and is sufficiently suggestive of their function as viewed from the patho- 
logical stand-point of the old humoralist. What we know of the action of these 
medicines at present amounts to this, that they modify the nutritive processes of 
the body. To deny, as has been done, the existence or value of medicines of this 
class because we cannot tell why mercury relieves syphilis or why potassium iodide 
cures rheumatism is as absurd as to deny the existence of the syphilitic and the 
rheumatic dyscrasia because we do not know their ultimate nature. 

PHOSPHORUS. 

Phosphorus is a translucent, when pure nearly colorless, but 
usually slightly yellowish, highly inflammable elementary body, 
which is tasteless, but possessed of a peculiar alliaceous odor. It is 
insoluble in water, sparingly soluble in ether, absolute alcohol, and 
the oils, freely so in chloroform. It takes fire at 100° F., and melts 
at 111.2° F. In the shops it is in cylindrical sticks, covered with a 
whitish layer, and having, when cut, a waxy consistence and lustre. 
It occurs in several allotropic forms, — red phosphorus, black phos- 
phorus, and the crystallized metallic phosphorus of Hittorf, whose 
physiological properties have not been investigated. 

Official Preparations : 

Phosphorus T ^ grain (0.6 Milligm.). 

Pilulae Phosphori Each T ^ grain (0.6 Milligm.). 1 pill. 

Absorption and Elimination. — It has been demonstrated that 
phosphorus passes into the blood as phosphorus, and not in the 
form of phosphoric acid or other compound. 

In cases of poisoning in men the breath is said to be sometimes distinctly phos- 
phorescent, and in animals Bamberger has found phosphorus in the blood, and 
Husemann and Marme in the liver two or three hours after its ingestion. W. Dyb- 
kowsky has detected it in the blood and liver ten hours after its ingestion, and 
other observers have demonstrated its presence in almost all of the tissues. It 
seems probable that to some extent it finds entrance into the circulation by being 
338 



ALTERATIVES 339 

dissolved in the various fatly matters contained in the alimentary canal. At. the 
temperature of the body, however, it yields abundanl vapors, and Bamberger lias 

demonstrated that these readily ami rapidly pass through animal membranes. He 

lias found that detibrinat cd blood, when separated from the fumes of phosphorus 
only by an animal membrane, rapidly becomes saturated with the poison. Dyb- 
kowsky has confirmed this, and it cannot be doubted thai in a similar manner living 
blood absorbs the poison from the alimentary canal. W. Dybkowsky's research 
renders probable the theory of Schuchardt that the phosphorus is converted to 
some extent in the alimentary canal, but much more largely in the veins, into phos- 
phuretted hydrogen, and that some of this compound and some of the phosphorus 
itself is oxidized in the venous blood, so that phosphoric acid, besides phosphorus 
and phosphuretted hydrogen, is emptied into the arterial blood; further, thai the 
last two compounds arc oxidized at the expense of the arterial blood and the tis- 
sues it feeds, and that the poisoning is due to this deprivation of oxygen. For the 
details of the experiments upon which these conclusions rest we must refer the 
reader to the original memoir.* According to Plaice, phosphorus is not found in 
free condition in these cases in the urine. 

Physiological Action.- The physiological action of phosphorus 
in therapeutic doses is probably entirely different from that which 
it exerts when in larger amounts. It is a constituent of most of the 
more important tissues, and is especially abundant in the nerve- 
centres, upon whose nutrition it is believed by many to act as a stimu- 
lant. So far as the nervous system is concerned, this assertion rests 
upon clinical observation; but Wegner (confirmed by S. Miura and 
W. Stoeltzner) has experimentally demonstrated such an action upon 
the bony tissues. When adult animals are fed upon minute doses 
of phosphorus the spongy tissue in the long and short bones becomes 
thickened and the compact tissue more dense. After a time new 
tissue is deposited upon the inside of the shafts of the long bones, 
in some instances until the marrow cavity is obliterated. ' The action 
upon the bones of growing animals is even more marked. 

For reasons already adduced (see page 338), it is certain that in 
poisonous doses phosphorus enters the blood in its elemental form. 
Wegner advances the following reasons for believing that thera- 
peutic doses act as phosphorus upon the bony tissues. First, no 
similar action can be obtained from phosphoric acid unless from eight 
hundred to one thousand times the proportional dose be given. 
Second, the newly formed tissue is at first gelatinous. Third, there 
is no excess of phosphates in the bone. Fourth, when the food is 
deprived of lime the same new tissue arises, but remains in a soft, 
gelatinous state. 

Therapeutics. — Phosphorus was at one time believed to be 
a diffusible stimulant, and it possibly may exert such an influence. 
In the acute nervous exhaustion of typhoid pneumonia we have once 
or twice seen it apparently act favorably in this way. The chief 
use of phosphorus in medicine is as a nutrient tonic to the nervous 
.-ystem. In all cases of chronic nervous exhaustion, whether involving 

* M. Lecorche" (Archives de Physiologie Normale el Patholopique, 1868, i.. 18G9, ii.) believes 
that phosphorus acts in the blood a" phosphoric acid, but docs not establish his opinion. For a 
discussion of this, see Dybkowsky's paper. 



340 GENERAL REMEDIES 

the cerebral or the spinal centres, it is of great value; even when the 
symptoms strongly suggest organic disease, as in threatening cere- 
bral softening or myelitic paraplegia from excessive venery, it is often 
of service. It has been strongly extolled in neuralgia due to nervous 
exhaustion. 

It is probable that it may be of value in some cases of impaired 
vitality although the nervous system be not obviously implicated. 
H. Eames states that he has obtained great benefit from its use in 
obstinate skin affections, such as lupus, acne, and psoriasis. S. R. 
Percy has used it successfully for repeated furuncular eruptions. 
It has also been asserted to be useful in cataract.* 

On account of its marked influence on the development of bone, 
Wegner suggested its use in osteomalacia and in rickets, and thereby 
started a large amount of clinical experimentation and a considerable 
clinical literature, in which there is some contradiction: the general 
result, however, has been to establish the value of the drug in rachitic 
cases, especially in those in which there is a tendency to osteoporosis. 
As large doses as can be borne without derangement of the digestion 
should be given. 

Toxicology. — The ingestion of a fatal dose of phosphorus is 
not followed by any sensible effects for some time. After, however, 
from three to twelve hours a sense of weakness and of general wretch- 
edness manifests itself, usually accompanied, or soon followed, by 
nausea and vomiting, and in most cases the patient soon complains 
of abdominal pain, the severity of which, however, never equals that 
of corrosive poisoning. The matters vomited consist of food, mucus, 
and bile. During the first eight or ten hours they often smell strongly 
of phosphorus, and are luminous in the dark. The vomiting may 
persist during the whole attack, but general^ there is an almost 
complete remission of symptoms on the second or third day. 

The tongue is whitish or abnormally red, sometimes furred. 
There are generally fever (Maukopff), loss of appetite, and thirst. 
Later in the poisoning there is very often a remarkable fall in the 
temperature, which is generally, but not always, a precursor of death. 
The lowest point we have seen noted was 31.2° C. (88.2° F.) some 
hours before death, f In some cases fever is altogether absent, or 
comes on just before death. $ 

The stools are at times normal in character and frequenc}^, but 
there is general diarrhoea or constipation, with flatulence. Late in 
the attack the passages are in most cases very light clay-colored, 
or even whitish, and exceptionally they are blood}'. In some cases 
they are phosphorescent. 

Jaundice comes on in from thirty-six hours (Maukopff and Tiingel) 
to five days (Lebert and Wyss) after the ingestion of the poison. 
In most cases it appears first in the conjunctiva, but sometimes the 

* Tavignot (Rerue de Thtrapeutique Medico-Chirurgicale, August and September, 1871) and 
Gioppi (Giornale d'0[talmologia, abstract in N. Y. Medical Record, 1872). 
t Battmann (Archiv der Heilkunde, 1871, 257). 
I Concato (Sydenham Soc. Year-Book, 1869-70, 454). 



ALTERATIVES 341 

urine gives previous warning of its approach. In some cases there is 
with it a decided and palpable increase in the size of the liver, which 
may pass, if the patient live long enough, into an equally apparent 
lessening of the bulk of that viscus. There is frequently pain and 
tenderness over the region of t he liver. The severe nervous symp- 
toms are rarely, if ever, developed until after the jaundice, although 
early in the attack there are not infrequently anxiety, headache, 
giddiness, and dreamy unquiet sleep, or even sleeplessness. The more 
pronounced nervous symptoms consist of delirium, which may be 
wild and is very frequently erotic, with somnolence ending in coma 
ami death, occasionally preceded by convulsions. According to 
Taylor, t he latter are a certain sign of approaching dissolution. 
Very generally partial spasms and fibrillary contractions of the volun- 
tary muscles occur, although there is always, in not too rapid cases, 
progressive paresis of the voluntary muscles. Death is usually put 
off beyond twenty-four hours, yet it has occurred in a child in four 
hours and in an adult in seven hours; also in nine hours. The patient 
may suddenly succumb to collapse and cardiac paralysis, but more 
commonly dies comatose from a gradual failure of respiration and 
circulation. 

If recovery occur it is by a gradual amelioration of the symptoms, 
and the health of the patient is apt to be impaired for some time, 
the most marked disturbances usually being the digestive and ner- 
vous symptoms. Apparently desperate cases will sometimes con- 
valesce unexpectedly, and Ti'mgel states that a favorable issue may 
take place even after violent delirium. 

The urine is almost always much affected by the poison. Very 
commonly it is scanty or albuminous, and sometimes it contains 
sugar.* As was first pointed out by Munk and Leyden, after jaundice 
has set in, bile-acids, as well as biliary coloring-matter, are always 
to be found in the urine. Not infrequently a cloudy sediment con- 
sisting in part of epithelial cells, often tinged with bile, is deposited. 
Oswald Kohts and other observers have found leucin and tyrosin 
in the urine of dogs poisoned with phosphorus, and undoubtedly 
these substances may occur. Wohlgemuth has found besides these 
bodies arginin in the urine of a rabbit poisoned with phosphorus. 
The albuminuria generally follows, but may precede the icterus. A 
very remarkable and apparently constant constituent of the urine is 
sarcolactic acid. Fat has been found in the urine inside of renal 
epithelial cells, and also as free globules (Schultz). 

In some instances phosphorus-poisoning presents symptoms quite different 
from the typical array. Death may take place in a few hours, and in such cases 
jaundice is not generally present. Zeidler reports a death in forty-two hours, from 
suppression of urine, with collapse and erotic delirium. In a case of Bollinger's 
the chief symptoms were vomiting, pain and tenderness over the abdomen, great 

* In only six of one hundred and forty-one consecutive cases of phosphorus-poisoning in the 
Medical Clinic of Prague was sugar found in the urine (Zeilschr. f. Heilkde. N. F., li. 8 u. 9, p. 339, 
1901 I. As originally stated by Von Jaksch, the sugar is probably of secondary origin, due to the 
alterations of the liver. 



342 GENERAL REMEDIES 

weakness of pulse, gradually developed paralysis of the legs, and death, without 
jaundice, in four and a half days. The autopsy revealed hemorrhagic effusion 
between the membranes and the spinal cord, and also into the sheaths of the 
proximal portions of the spinal nerves. 

In women, fatal doses of phosphorus very commonly produce a bloody pseudo- 
menstrual discharge, or, when pregnancy exists, abortion. M. Miura lias found 
in the foetus of poisoned rabbits structural changes similar to those of the mother. 

Sub-acute phosphorus-poisoning is said sometimes to be manifested by 
symmetrical gangrene of the extremities. (See W. K. W., 1901, No. 52.) 

Post-Mortem Appearances. — The most characteristic lesions found 
after death from phosphorus-poisoning are wide-spread fatty degen- 
erations involving practically all of the organs, but especially marked 
in the gastro-intestinal mucous membrane, the liver, and the kidney; 
an inflammation of the glands around the pylorus; and hemorrhagic 
extravasations. 

As was first pointed out by Virchow, there is universally a gastro-adenitis, 
which causes the gastric mucous membrane to become thickened, opaque, whitish, 
grayish, or yellowish-white. This gastro-adenitis is not due to a local action of the 
phosphorus, because it occurs when the poison is introduced through other channels 
than the mouth. The duodenum and intestines suffer similar changes. 

The liver is generally very much enlarged, friable, and light-colored; some- 
times it is mottled, and sometimes portions of it are deeply stained with bile.* The 
cells are gorged with fat-globules, f and in some cases there are small-celled inter- 
stitial thickenings due to hyperplasia of the trabecular tissue. The gall-bladder 
may be full or empty. In protracted cases the liver undergoes atrophy, with destruc- 
tion of its secreting cells. According to the researches of Arthur Heffter, the 
percentage of lecithin in the liver, which is fixed in health, is greatly lessened in phos- 
phorus-poisoning. The kidneys, especially in their cortical portion, suffer a degenera- 
tion similar to that of the liver, the epithelium becoming enlarged, granular, fatty, 
and finally undergoing destruction. The voluntary and cardiac muscles, the spleen, 
the lungs, and probably all the tissue, partake of the universal fatty degeneration J 
which Wegner has shown to involve even the minute arterioles. 

The nervous system does not escape. As long ago as 1880 Danillo declared 
that he had found a myelitis in phosphorus-poisoning, and Gurrieri has discovered 
in the poisoned dog degenerations of various portions of the spinal cord; while it 
has been shown by Uziemblo that profound alterations take place in the retina, 
which becomes cedematous, with marked alterations in the vessels, hemorrhagic 
extravasations, and necrotic degeneration of the nervous cells. 

The blood is often profoundly affected (Taussig and Corin and Ansiaux), 
becoming very dark, more or less completely losing its power of coagulation, and 
apparently suffering also in its corpuscular elements; ecchymoses are almost uni- 

* According to researches made by Emile Rousseau in the Pathological Laboratory of the 
University of Pennsylvania, the first anatomical changes in the liver occur in the centre of the 
lobules around the hepatic vein. 

t A. Lebedeff {Arch. j. Physiol., 1883, xxxi. 11) believes that the fat in the liver is not pro- 
duced by degeneration of the hepatic tissue, but has simply been transported there from the sub- 
dermal regions. He bases this opinion upon his own observations, — first, that the phosphorus fat 
has the same chemical constitution as has subdermal fat; second, in a dog which had been fed 
with linseed oil and then poisoned with phosphorus, the liver was loaded with linseed oil. This 
evidence is of very little value, because on the one hand the linseed oil probably accumulated in 
the dog's liver before the poisoning and simply remained over, and on the other hand there is no 
proof that fat produced by degenerative changes necessarily differs in composition from other fat. 
The fact that the liver and other organs are destroyed in phosphorus-poisoning may be considered 
proof that the fat is formed out of the affected tissue; although this seems contrary to the allegation 
of Bergeat (Gesellsch. f. Morph. u. Physiol. Miinchen., 1888), that in very emaciated animals the 
phosphorus-poisoning may run its course without the formation of fat. 

I For full discussion of the pathology of phosphorus-poisoning, see Ziegler (Beitrage Path. 
Anat., ii.), G. Kronig (Virchow's Archiv, 1887, ex.), Aufrecht (Dcutsch. Arch. Klin. Med., 1897, 
lviii.), Hans Schmaus, (Milnchener Med. Wochensch., 1897, xliv , also 1898, xlv.), Hans Schmaus 
and Arthur Boehm (Arch. f. Path. Anat., 1898, clii.). See also Schmidt's Jahrbiicher, eclvii., 94. 



ALTERATIVES 343 

venal, and he mat in crystals are occasionally found in the viscera. The ecchymoses 
occur in all parts of the body, but arc apt to he especially pronounced in the medi- 
astinum and the scions membranes. Schiff has found that, in dogs, after death 
from phosphorus, the blood docs not pass into I he veins, hut remains in the arteries. 
0. Silbermann states thai thrombi arc formed in the blood-vessels; and it has been 
shown by ('<■ Puppe that these are very common in slow cases of the poisoning, 
and are of fatty nature. 

It should be remembered that although some or all of the lesions which have 
just been described are usually found in the bodies of persons dead of phosphorus- 
poisoning, it is possible for the poison to take life very rapidly and leave no trace 
of its influence, there being not even sarcolactic acid in the urine (see case reported 
by Paltauf). According to the researches of VV. W. I'odwyssotsky, in rapid cases 
the fust change in the body consists in the formation of little whitish-yellow ne- 
crotic foci in the liver. 'The anatomical changes in the liver in phosphorus-poison- 
ing are sufficient to confirm the statements of Schultzen and Riess, that in the 
poisoning there is arrest of glycogen and sugar formation. 

The elimination of bile acids in the urine shows that the jaundice of phos- 
phorus is caused not by an arrest of secretion, but by an occlusion of the biliary 
passages and consequent resorption of the bile.* O. Kohts lias apparently demon- 
strated that the occlusion is most frequently due to the duodenitis involving the 
common duct, so as to obliterate its lumen by the swelling of the mucous membrane. 
In some cases, however, it is probable, as believed by Wyss, Alter, and Ebstein, 
that a catarrhal inflammation of the minute gall-ducts is the cause of the jaundice, 
and also that the result is in part, effected tlu-ough pressure upon those ducts by the 
swelling of the glandular and trabectdar tissue. It is proper to state that Demar- 
baix and Willmart insist that the icterus is not really hepatogenous, but hemic in 
origin, chiefly because they have found hematoidin in the urine. This fact, however, 
proves only that the blood is altered by the poison; it does not disprove the liver 
origin of the jaundice. 

Diagnosis. — Acute phosphorus-poisoning so closely resembles 
yellow atrophy of the liver that their clinical distinction is sometimes 
difficult, nay, impossible. Distinct phosphorescence in the breath, 
vomit, or stools would, of course, be direct evidence of poisoning. 
This phosphorescence, however, very often cannot be detected: 
according to Vetter, it can be rendered more evident in the vomit, 
stools, etc., by acidifying with sulphuric acid and warming in a shal- 
low dish. When death ensues during the first week of phosphorus- 
poisoning, the enlarged liver affords a distinctive proof of poisoning; 
but when the case is more protracted, the atrophied liver of phos- 
phorus cannot be distinguished from that of the natural disease. 
Phosphorus-poisoning usually develops more abruptly than does 
acute yellow atrophy, and the primary disturbance of the stomach is 
more severe, while the lull of the symptoms is more complete. The 
clinical differences, however, between various cases of either affection 
are greater than those which have been relied upon as separating the 
two affections. Kohler has asserted that oxymandelic acid in atrophy 
of the liver replaces the sarcolactic acid of phosphorus-poisoning, and 

* E. Stadelmann (Archiv f. Exper. Path. u. Pharm., 1888, xxiv.) states, as the result of his 
experiments made upon dogs, that so far as the secretion of bile is concerned three stages can be 
made out. In the first stage there are irritation of the liver and increase of the formation and 
excretion of biliary coloring-matter; in the second stage the gall becomes mucous and cloudy, and 
the production and separation of biliary coloring-matter are lessened (it is in this stage that the 
icterus begins); in the third stage the gall becomes again clear, dark, and more rich in biliary 
coloring-matter, so that the normal excretion of biliary coloring-matter is notably surpassed. 



344 GENERAL REMEDIES 

stress has been laid upon the asserted facts that in the natural disease 
leucin and tyrosin are present in abundance in the urine, while in 
the poisoning they are absent. In j'ellow atrophy, however, tyrosin 
is not infrequently absent from the urine and leucin present in very 
small amount, while both principles may be present in phosphorus- 
poisoning.* In regard to the acids in the urine, very careful chemical 
analysis would in any case be necessary to determine their presence, 
and sufficient evidence is certainly not yet forthcoming to show that 
either of them is really characteristic. Chemical examination is 
therefore absolutely necessary in all medico-legal cases, f According 
to M. Poulet, phosphorus is eliminated as hypophosphoric acid, and 
the poisoning can be recognized by heating the urine with nitric acid to 
calcination. If hypophosphoric acid be present, as dryness is reached 
the mixture suddenly bursts into a flame like a packet of matches. 

The cause of death in phosphorus-poisoning is probably the 
wide-spread structural alterations, as the experiments of A. Hauser 
indicate that the poison does not act by inhibiting life processes. 

In the very acute cases of phosphorus-poisoning a primary con- 
dition of pronounced cardiac weakness, passing into paralysis, may 
be present (Pal); in the subacute cases the heart-muscle undergoes 
so much degeneration that a slowly developed but progressive cardiac 
weakness is produced and may be the cause of death. 

Treatment. — The indications for treatment in phosphorus-poison- 
ing are very evident. It is plain that no medication can influence the 
terrible organic lesions induced, and that the primary object must 
be to prevent the absorption of the poison. Emetics and purgatives 
are, therefore, of prime importance. The necessity of the persistent 
use of evacuants is shown by the finding of phosphorus by Starck in 
the stools three and a half days, and in the vomit two days, after the 
ingestion of the fatal dose. As phosphorus is soluble in oils, no fatty 
matters should be allowed either in the food or in the medicines. 
The most valuable antidotes are copper sulphate and potassium 
permanganate. As an emetic, copper sulphate should always be chosen. 

The oil of turpentine, originally proposed by Andant as an antidote to phos- 
phorus, has been largely used by experimenters, with apparently contradictory 
results, which, as is now known, were due to the employment of different varieties 
of the oil. 

Ordinary American oil of turpentine and Canada balsam are of no value in 
phosphorus-poisoning. 

There are in European commerce three varieties of turpentine, — the rectified, 
the German, and the French. Jonas found that, while the pure oil has no effect 
upon phosphorus, the acid French oil forms with it a crystalline, spermaceti-like 
mass. This is soluble in ether, alcohol, and alkaline solutions, and has received 
the name of turpentine-phosphoric acid. It is said to be eliminated by the kidneys 

* Cases (Wiener Med. Presse, 1872; Schmidt's Jahrb., clxix. 127, cxcv. 123). Ossikovsky 
believes that the principles appear habitually about the sixth day of the poisoning, when the liver 
is still enlarged. 

t For discussions of the diagnosis between yellow atrophy and phosphorus-poisoning, see 
Kohler (Syd. Soc. Year-Book, 1870, 455), Schultzen and Ries (Annalen des Berlin. Krankenhauses, 
1869, xv.), and especially I. Ossikovsky (Wien. Medizin. Presse, 1872, xiii., abstracted in Schmidt's 
Jahrb., cliv. 15). For cases in which the question was legally raised, investigated, and discussed, 
see Schmidt's Jahrb., cxli. 167; Syd. Soc. Year-Book, 1832, 430; Annates d'Hyoiene, Jan. 1869. 



ALTERATIVES 345 

unchanged, and to exert do deleterious influence. The elaborate experiments of 
Yet tor on dogs and rabbits gave results in accord with (hose facts, for he found the 
rectified and German oils to be of no value in phosphorus-poisoning, while the crude 

acid French Oil was distinctly antidotal, kochler, however, asserts that- when the 
German oil has not been rectified for some time, it acts upon phosphorus. He 
believes that the oil acts partly by oxidizing the poison and partly by converting it 
into the harmless turpentine-phosphoric acid. One part of the oil must be given 
for 0.01 part of the phosphorus.* See also Bene. 

As was pointed out by Eulenburg and Guttmann, and subsequently by Bam- 
berger, phosphorus in a solution of a soluble salt of copper becomes immediately 
black, owing to the formation of a phosphide of the metal. Bamberger also asserts 
that, while this change is very rapid, that induced by turpentine is a slow one, 
and, from an elaborate series of experiments upon animals, concludes that copper 
i-. much the more valuable and certain antidote. Antal appears to have been the 
first to use potassium permanganate as an antidote to phosphorus, and in a series 
of experiments upon dogs E. Q. Thornton found it much superior to cupric sulphate. 
Hydrogen dioxide appeared in Thornton's experiments to be valueless. In human 
poisoning cupric sulphate should be given in dilute solution, three grains every 
five minutes until vomiting is induced. After this the potassium permanganate 
should be freely administered, or, as was successfully done by Hajinos, the stomach 
may be washed out with its solution; later, the magnesium sulphate or citrate 
may be given as a quickly acting purge, and symptoms met as they arise. f 

Chronic Poisoning. — Match-makers and other artisans who are 
exposed by their occupations to the fumes of phosphorus suffer 
from chronic poisoning, which is especially distinguished by the 
occurrence of necrosis of the upper or lower jaw. It occurs chiefly 
in those artisans who have bad teeth, and the experiments of Wegner 
have demonstrated that the necrosis of the jaw is due to the local 
action of the vapor of phosphorus. J 

Wegner found that when rabbits were kept in an atmosphere full of the fumes 
of the poison no necrosis ever occurred, unless, by means of an unsound tooth or 
an artificial wound, the atmosphere had access to the bone. If such access were, 
on the other hand, allowed to any bone of the body, periostitis and subsequent 
necrosis resulted. Further, when rabbits received continuously small doses of the 
phosphorus by the mouth, no necrosis occurred even after wounds which laid bare 
the bones. 

Administration. — The dose of phosphorus may be set down as 
from the one-hundredth to the one-fiftieth of a grain (0.6-1.3 

* For a case of recovery see Guy H. R., xxvi. 13. 

t We have allowed the text to stand as in the old edition because of the present uncertainty 
as to the comparative values of the use of copper sulphate and potassium permanganate. In the 
United States phosphorus-poisoning is very rare: we have not met with more than one or two 
reported cases. In Continental Europe, however, probably on account of the difficulty of obtaining 
poisons through the restrictions of the law, phosphorus is perhaps the most used of any poison for 
the purpose of suicide. Thus, out of forty cases of attempted self-murder, brought to the Prag 
clinic between 1889 and 1895, in thirty-nine the phosphorus contained in the heads of matches had 
been employed (Fr. Lanz, Bert. Klin. Wochenschr., 1895, xxxiii.). Formerly the treatment at the 
clinic consisted in washing out the stomach with warm water until the smell of phosphorus dis- 
appeared; then continuing the washing with water containing copper sulphate and calcined mag- 
nesia, and following up by giving internally copper sulphate and oil of turpentine; also large doses 
of sodium bicarbonate. Since 1893, when the Antal method was introduced, the plan has been to 
wash out the stomach with large quantities of one-eighth-per-cent. solution of the permanganate; 
then administer one litre of the one-half-per-cent. solution, at the same time giving a purgative; 
on the following day giving large doses of sodium bicarbonate with the oil of turpentine. The 
mortality per cent, of the cases before the change of treatment was 36.0; since the change of 
treatment, 41.6 — a result which is not favorable to the newer method. 

X In the manufacture of matches, phosphorus sesgviszdphide, P4S3, has been largely substituted 
for yellow phosphorus, and is believed to be only slightly toxic. For a study of it, see C. G. 
Santesson (V\ V. N. K. I. St., July. 1902). 



346 GENERAL REMEDIES 

Milligm.), increased unless gastric disturbance is produced. J. A. 
Thompson affirms that he has given one-fourth of a grain every four 
hours without injury. Anstie says that he has seen slight poisoning 
produced by three-fourths of a grain taken in seven days in divided 
doses. It is always wiser to have a freshly made preparation, as 
phosphorus in solution or in pill is very prone to undergo oxidation. 

Zinc Phosphide has been largely used, with asserted good results, 
as a substitute for phosphorus. According to the researches of Vigier, 
it would seem that the phosphide yields its phosphorus within the 
economy, probably to form a phosphuretted hydrogen. He found 
that it killed rabbits more quickly than did a corresponding dose of 
phosphorus, and that both symptoms and lesions were identical in 
the two cases. The phosphide should be given in pill or granule. 
Dose, one-twentieth to one-twelfth of a grain (3-5 Milligm.). 

ARSENIC. 

Metallic arsenic is not employed in medicine. The substance 
ordinarily referred to as arsenic in medical parlance is arsenous an- 
hydride, As0 3 , known officially as arsenic trioxide. This substance, 
which is sometimes incorrectly known as arsenous acid, is obtained 
as a by-product in smelting, from certain European ores, notably 
the cobalt ores of Germany and the iron ores of England. It occurs 
either as transparent glass-like pieces or in the form of a white crystal- 
line powder. It is slightly soluble in water, requiring at ordinary 
temperatures from thirty to one hundred parts of water, according 
to various conditions, to dissolve it. It is odorless and almost taste- 
less, but when heated it emits a garlicky odor owing to its first being 
reduced to a metallic state and then volatilized. 

Besides the anhydride, the U. S. Pharmacopoeia recognizes the 
iodide of arsenic and also sodium arsenate, and a solution of potas- 
sium arsenite. Arsenic iodide is an orange-red crystalline powder 
soluble in twelve parts of water, which is decomposed by light. It 
is comparatively rarely employed. Sodium arsenate, Na 2 HAs0 4 , 
when dry, is an amorphous white powder freely soluble in water, 
odorless and with a faintly alkaline taste. It takes up seven 
molecules of water and forms colorless transparent crystals. 

Official Preparations : 

Arseni Trioxidum fa to fa grain (1-3 Milligm.). 

Arseni Iodidum fa to fa grain (3-6 Milligm.). 

Sodii Arsenas fa to \ grain (5-10 Milligm.). 

Sodii Arsenas Exsiccatus fa to fa grain (3-6 Milligm.). 

Liquor Acidi Arsenosi (1 per cent.) 5 to 10 minims (0.3-0.6 C.c.). 

Liquor Sodii Arsenatis (1 per cent.) 5 to 10 minims (0.3-0.6 C.c). 

Liquor Potassii Arsenitis [Fowler's Solution] 

(1 per cent.) 5 to 10 minims (0.3-0.6 C.c). 

Liquor Arseni et Hydrargyri Iodidi [Dono- 
van's Solution] (1 per cent, each of Arsenic 

and Mercuric Iodides) 3 to 5 minims (0.2-0.3 C.c). 



ALTERATIVES 347 

Physiological Action. — Local Action. — When in concentrated 
form arsenic is a powerful though slowly acting escharotic, and even 
when well diluted is a violent irritant. Although a violent poison to 
all forms of life, it acts proportionately so much more powerfully 
upon the higher than upon the lower organisms that it cannot be 
classed among the practical germicides. Johannsohn and Schaefer 
and also Boehm state that it exerts no influence upon non-organized 
ferments, either vegetable or animal, such as aniygdalin, pepsin, 
and pancreatin. 

Absorption and Elimination. — Although when arsenic is taken 
into the stomach in lumps it may be absorbed so slowly as to escape 
in part through the alimentary canal, when it is taken in powder, 
and especially when it is in the form of the soluble salt, it is absorbed 
with rapidity. 

It is eliminated chiefly by the kidneys, but it is thrown off freely 
when in toxic amount by all the excretory glands and mucous mem- 
branes, especially by those of the gastro-intestinal tract. The single 
dose escapes rapidly from the body, elimination being usually com- 
plete in from a few hours to three or four days. When in large amount 
it may remain long in the body. 

It is so readily taken up that its free external use and its employment as an 
escharotic are accompanied by distinct danger. Six cases are on record in which 
severe or fatal poisoning has been produced by the introduction of it into the vagina.* 

M. G. Bouchet and Lewald in independent researches found arsenic in notable 
quantities in the milk of nursing women. f Unterberger has detected it in the ali- 
mentary canal of animals poisoned by injection into the vein. M. Chatin has found 
it in the serosity of a blister, Bergeron and Lemattre in the sweat, and Taylor in 
the contents of the stomach of a child poisoned by its application to its scalp. 

Flandin and Danger failed, three days after the last dose, to detect arsenic in 
the bodies of animals to which fifteen grains had been given daily; and in a child 
killed in two days by an arsenical pigment, none of the metal could be found in 
the body. In the great majority of instances, however, there is no trouble in find- 
ing arsenic in the bodies of those poisoned by it, and Steinhauser reports a case in 
which it was detected in the remnants of a corpse that had been buried for twenty- 
two years. Further, it would appear that the failure to find arsenic has often de- 
pended upon the lack of delicacy in the chemical operations. Using the chemical 
method devised by Charles R. Sanger, E. S. Wood has been able to detect arsenic 
in the urine ninety-three days after the taking of a single toxic dose, and from sixty 
to eighty days after mild courses of Fowler's solution. 

General Action. — As arsenic is never used in medicine for an acute 
effect, the chief interest to the therapeutist centres around its physio- 
logical action when given in small doses; yet it seems necessary here 
to take cognizance of the physiological action of large amounts of 
the poison. % 



* See A. Haberda (Wien. Klin. Wochenschr., 1897, x. 9, 201). 
t See American Practitioner, 1887 



X The theory of Binz and Schulz, that arsenous acid acts by taking from protoplasm oxygen, 
so as to be converted into arsenic acid, and afterwards yields this oxygen to oxidize the protoplasm, 
and then repeats the process, seems to be so illy supported that in regard to it the reader is simply 
referred to Arch. f. Exper. Path. u. Pharm., xi., xiv., xxxvi.. xli.; also Brit. Med. Journ., 1882, ii. 
1135. Dogiel's theory, that arsenic unites chemically with the albuminous principle, is more 
probable. (See Trans. International Congress, 1884, i„ 134.) 



348 GENERAL REMEDIES 

Nervous and Muscular System. — Arsenic acts powerfully upon the 
nerve-centres, and to a distinctly less extent upon the nerve-trunks. 

In the frog arsenic acts as a paralyzant of the nerve-centres. W. Sklarck, of 
Berlin, states that the small dose causes in the frog cessation of voluntary movement, 
with complete loss of sensibility to chemical and mechanical irritants at a time when 
the animal will struggle actively to recover its position if laid upon its back. Tying 
of the iliac artery had no effect in preserving motion or sensibility in the protected 
leg. It would appear, therefore, that the cessation of voluntary motion was due to 
a complete paralysis of the centres of common sensation, probably up to the per- 
ceptive centre in the brain; the frog, placed upon his back, being induced to struggle 
into the normal position by sensations received either through the special senses 
or possibly through the muscular sense. The researches of Ringer and Murrell 
upon frogs yielded very different results from those just described, they found that 
the symptoms of poisoning came on only after the lapse of some hours, and that 
paralysis of voluntary motion preceded that of sensation and reflex action. Ringer 
and Murrell suggest that these differences of result depend upon the time of year 
at which the frog was experimented on. 

Circulation. — The toxic dose of arsenic greatly lessens the rate and 
force of the pulse-beat and markedly lowers the blood-pressure. 
Sklarck found that in the isolated frog's heart arsenic produces slow- 
ness and feebleness of pulsation, ending in a diastolic arrest, after 
which immediate galvanic or mechanical irritation caused imperfect 
systolic movements. It would appear, therefore, that the toxic dose 
of arsenic is a direct cardiac depressant; but as both Cunza and 
Unterberger have found that in arsenical poisoning the heart persists 
in its movements after the cessation of respiration, it is evident that 
arsenic is more powerful as a respiratory than as a circulatory poison. 
Further, as demonstrated by Unterberger, the lowering of the arterial 
pressure in arsenical poisoning is largely due to a vaso-motor paralysis. 

Thus, Unterberger found that in an animal under the influence of the poison 
neither galvanization of a sensory nerve nor of the vaso-motor centre in the upper 
cord had any influence upon the force of the blood-current. Galvanization of the 
splanchnics had no effect upon the arterial pressure, — apparently showing that the 
vaso-motor palsy was peripheral; but Unterberger found, to his astonishment, that 
stimulation of the cervical sympathetics had the usual effect upon the vessels of the 
rabbit's ear. Supposing these observations to be correct, there are only two seem- 
ingly possible methods of reconciling them: either the drug acts upon the peripheral 
vaso-motor nerves in the abdomen and not upon the same nerves in the neck, or else 
there is during arsenical-poisoning such depression of the power of the cardiac 
muscle that narrowing of the blood-path does not have the usual effect. Unter- 
berger found that compression of the abdominal aorta was followed by a great rise 
of pressure, and therefore he believes that the heart in arsenical-poisoning has not 
lost its power. Some complicated transfusion experiments which he made indicated 
differently; so that while his proposition that arsenic paralyzes the peripheral vaso- 
motor nerves of the abdomen and not those of the head may be considered prob- 
able, it certainly is not proved. It would be a very easy matter to decide the 
question by dividing the splanchnic nerves in a poisoned animal: if the reduction 
of the arterial pressure be really due to an abdominal vaso-motor paresis, section 
of the splanchnic should have no effect on it. 

Tissue-Change. — Schmidt and Stiirzwage believe that arsenic 
markedly influences tissue-change, because they found in rabbits a 



ALTERATIVES 349 

decided diminution in the excretion of carbonic acid and of urea 
during the use of minute doses of the poison. Fokker, however, was 

unable to perceive in three experiments that daily doses of from .15 
to .1)7.") grain of arsenic to a dog had any effect upon the elimination 
of urea, and Kossell and (<aethgens, in two experiments, have noted 
a very decided increase of the elimination of urea produced by toxic 
doses of arsenic in the dog. The experiments of Chittenden and 
Cummins are in accord with the early results of SUirzwage, as they 
found that in the case of rabbits arsenous acid has a tendency to 
diminish the elimination of carbonic acid. The evidence which we 
have at present is not sufficient to warrant a positive opinion, but 
it indicates that small doses of arsenic check tissue-change and decrease 
nitrogenous elimination, while large toxic doses have the opposite effect. 

Blood. — As arsenic is frequently used in various forms of anemia 
much interest is attached to its effect upon the formation of blood- 
corpuscles. Stockman and Charteris have found that repeated small 
doses of arsenic cause an increase in the formation of the leucoblastic 
cells of the bone marrow, with consequent stimulation of the forma- 
tion of white blood-corpuscles, but without marked change in the 
number of red cells. Larger doses produced a hyaline degeneration 
of the bone marrow with a decrease in the number of both white and 
red cells. 

Skin. — The changes in chronic arsenical-poisoning, especially as 
shown in the epidemic which occurred in Manchester, in 1900, as the 
result of contaminated beer, bear out the conclusions of clinical 
experience, that arsenic has a marked effect upon the nutrition of 
the skin. According to Brook, the most characteristic changes in the 
skin in this epidemic were the deposit of pigment and stimulation in 
the growth of the epithelium, similar changes occurring also in the 
modified dermal tissues, such as the finger-nails. 

Action of Small Doses. — Minute quantities of arsenic may be given 
for a long time without perceptible effect. When the dose is increased, 
active manifestations of gastro-intestinal irritation may appear, 
such as loss of appetite, nausea, abdominal pain or uneasiness, diar- 
rhoea, and perhaps sympathetic headache. By the use of frequent 
small doses these symptoms may generally be avoided, and what 
may be termed the constitutional action of arsenic be obtained. 
The earliest sign of this is generally a puffiness about the eyes, at first 
visible only in the early morning, but soon increasing into decided 
oedema, which after a time may lose its local character and general 
anasarca develop. This anasarca, as was, we believe, first pointed 
out by S. Weir Mitchell, may or may not be preceded or accompanied 
by the presence of albumin and of tube-casts in the urine. Beyond 
the production of the symptoms spoken of, arsenic should never be 
pushed in medicine. 

Therapeutics.— When arsenic is administered in small repeated 
doses, it may act as a stomachic, by slightly irritating the stomach 
and thereby provoking an appetite; and in certain cachexias it 



350 GENERAL REMEDIES 

increases the muscular strength and the general vigor. The history 
of arsenic-eating indicates that the drug has some positive tonic 
influence over nutrition; and although the increase of strength and 
of blood caused by its use in cachexias may be due to some indirect 
action of the drug, — for example, to a removal or overcoming of the 
morbific agent of the disease, and a consequent allowing of the re- 
cuperative powers of the system to assert themselves, — there is 
much reason for believing that the drug does act as a direct stimulant 
to nutrition. All that we know of the effect of arsenic upon the s} r stem 
throws only enough light on its therapeutic action to enable us to 
class it as an alterative, — a modifer and often an improver of 
nutrition. 

After very much discussion * it seems to be established that many of the Sty- 
rian peasants use arsenic habitually in large quantities; the young girls to beautify 
their complexions and enhance their charms; the men with the belief that it will 
increase their "wind," endurance, and sexual powers. The best authorities state 
that the arsenic-eating is practised chiefly in the northern and northwestern parts of 
Styria: that the white arsenic is preferred, the yellow commercial article being 
sometimes taken; the native red arsenic, or orpiment, very rarely; and that the 
commencing dose is about 0.22 grain, which is very slowly increased to 0.62 grain 
avoirdupois. f 

Among the diseases which clinical experience demonstrates are 
especially benefited by the use of arsenic is chronic malaria. No one 
would at present think of employing the drug in acute remittent fever, 
or even in acute intermittent, unless under very peculiar circumstances. 
It is in those cases which have resisted quinine, in which the par- 
oxysms have become irregular, returning at long intervals, and in 
which the anemia and the general nutritive disturbance are even 
more prominent than the febrile disorder, that arsenic is especially 
valuable. In these cases it should be administered with sufficient 
boldness, very generally in conjunction with iron. George B. Wood 
recommended that the first doses should be as large as the system 
will endure, so as to make a decided impression at once. When the 
ague paroxysms are frequent it is perhaps well to employ this plan; 
but when it is the cachexia rather than the active disorder that is 
to be combated, it is preferable to commence with small doses and to 
increase them until some constitutional symptom is produced. In 
ordinary inter mittents, after the paroxysms have been broken up by 
quinine, it is very well to place the patient upon a preparation of 
arsenic and iron, as a prophylactic against their return. When, 
in ordinary intermittent fever, for any cause quinine cannot be admin- 
istered, arsenic may be employed. In these cases, as already inti- 
mated, the first dose should be large, so as to make an immediate 

* See Vogt (Lehrbuch der Pharmacodynamik, Aufl. iii. i.), Charles Heisch (Pharm. Journ. 
Trans., 1859 and I860, i. 556; British and Foreign Med.-Chir. Review, xxix. 144), and C. Maclagan 
(Edinb. Med. Journ., 1864, 203; Edinb. Med. and Surg. Journ., 1871, xvi. 569). 

t The experiments of Cloetta (A. E. P. P., liv. 196) indicate that the tolerance to arsenic is 
based on impeded absorption. In the dog, which has developed high resistance to arsenic given by 
mouth, the susceptibility to the metal, injected hypodermieally, is not diminished. 



ALTERATIVES 351 

impression; from five to ten minims of Fowler's solution, properly 
diluted, may be given every two or three hours until some decided 

symptom is produced. When the stomach refuses the remedy, it 
has been recommended by Boudin to give it by the rectum, which 
he a (linns will often hear even a grain of the acid. Not more than a 
third of this amount should, however, be used as a commencing dose. 
In malarial intermittent neuralgia, arsenic may be employed as a 
very useful adjuvant to the antiperiodic alkaloids. K. M. Downie 
calls attention to the value of arsenic as a prophylactic against malaria. 
His trials were not numerous enough to be conclusive, but so far as 
they go they indicate that arsenic is even superior to quinine. 

It is alleged that arsenic injected directly into the growth is an 
effective remedy in lymphatic tumors, especially in the affection known 
as malignant lymphoma* 

In various skin diseases arsenic is a valuable remedy. According 
to Duhring it affects the epidermis generally by its influence upon 
nutrition. It is more commonly useful in those skin diseases involv- 
ing the superficial strata of the integument. As it is a stimulant it 
should ordinarily not be employed in the acute inflammatory stages 
of skin disease, when there is burning, itching, and rapid cell change. 
Its greatest use in skin diseases is in the chronic conditions, as in 
psoriasis and in eczema, especially of the chronic squamous and 
papular varieties, and where the disease is superficially seated. 

Pemphigus is generally favorably influenced and often relieved 
or cured by its use. It should be prescribed cautiously but fearlessly, 
large doses usually being required. It is the most reliable remedy for 
this disease. In lichen it is usually employed with great advantage, 
especially in lichen planus, in the rare lichen ruber of Hebra, and in 
allied diseases. Occasionally it may be given with benefit in chronic 
urticaria. 

It may prove of value in certain cases of a-\ie and comedo, especi- 
ally in chronic small papular acne, in neurotic cases. In certain 
glandular hypersecretory diseases, as seborrhea and hyperidrosis of 
neurotic origin, it is also useful. Before prescribing it the digestive 
tract should be carefully looked into, and if disordered in the slightest 
degree should first be rectified. This observation holds good for its 
use in all diseases of the skin. In morphaa, alopecia areata, and other 
atrophic diseases it is also sometimes of value. If improvement 
follows its use it is usually best to allow the patient to continue with 
the treatment for some time after all symptoms of the disease have 
disappeared. 

Arsenic is a very valuable remedy in the treatment of chronic 
bronchitis, and is often of the greatest service not only in chronic 
pneumonia, or so-called fibroid phthisis, but even in true tubercular 
phthisis when the course is very slow and chronic. In asthma it may 
be given internally and also used locally. (See Expectorants.) 

See Wien. Med. Wochenschrifl, 1871; Archiv f. Klin. Chir.. xviii.; Strieker's Jahrb., 1877. 



352 GENERAL REMEDIES 

In certain nervous diseases arsenic acts very favorably, in some 
unknown way. In chorea it has acquired a deserved reputation. In 
this affection iron and other tonics are generally indicated and may 
be given consentaneously with the arsenic. It is best, however, to 
administer the latter separately, as the dose must be steadily increased 
until oedema or other manifestations betray a decided action. Arsenic 
has from time to time been strongly recommended in whooping- 
cough, non-malarial neuralgia, and simple gastralgia, or gastric 
neuralgia. 

Arsenic is of value in those forms of chronic rheumatism in which 
potassium iodide is commonly employed. It is often advantageous to 
alternate, administering one of these alteratives for three or four 
weeks, and then the other for the same length of time. In rheumatic 
gout, or rheumatoid arthritis, it has been highly extolled. 

Toxicology. — When a single dose of arsenic of just sufficient 
size to be felt is ingested, colicky pains, diarrhoea, and perhaps nausea 
result. After a very large toxic dose, in from one-quarter to three- 
quarters of an hour an intense burning pain is felt in the oesophagus 
and stomach, soon spreading to the whole belly, and often accom- 
panied by a sense of constriction at the throat and an acrid, metallic 
taste. In a very short time violent vomiting and purging come on. 
The matters rejected are at first mucous, and variously colored by 
the contents of the primae viae; but they soon become bilious, often 
yellowish or greenish, and finally serous, with mucoid flakes and a 
greater or less amount of blood. As the case progresses the symptoms 
mentioned increase in intensity, and to them are soon added others 
of different nature. The thirst is excessive; the urine is suppressed; 
the extremities are icy cold; the pulse is small, feeble, and frequent; 
the rapid and labored respiration is very much embarrassed and 
painful from the abdominal tenderness; the surface is dark and cya- 
nosed; violent cramps add their torture; exhaustion deepens into 
collapse; convulsions or coma ensue, and death occurs in from five 
to twenty hours. 

In another set of cases, when the dose has been smaller, or the 
subject less susceptible, the termination is not reached so soon. After 
symptoms, similar to but less violent than those just described, 
have lasted from a few hours to one or two da) r s, a remission occurs; 
the purging and vomiting grow less frequent, or perhaps intermit; 
even the abdominal tenderness may in great measure disappear; 
but the persistent thirst, cold extremities, and albuminous urine show 
that the danger is not past, and after a time the case puts on a more 
alarming aspect. Fever develops, the tongue becomes dry and red, 
the belly very tumid, the abdominal pain more severe, dyspnoea and 
cyanosis occur, the face is swollen, nervous symptoms, tremblings, 
cramps, and convulsions appear, and finally an icy coldness pervades 
the frame, and death occurs in from two to six days. The mind is 
generally clear to the last. An eruption very frequently appears. 



ALTERATIVES 353 

sometimes as early as the second day, sometimes not until the fifth. 
Its character is various: thus, it may be petechial, urticaria-like, 
papular, vesicular, or pustular.* 

Such are the ordinary phenomena of acute arsenical-poisoning; but anomalous 
oases are not very rare. Immediate profound collapse, without abdominal pain, 
is said to have been the chief manifestation in some eases. We have seen heavy 
sleep as the most marked symptom, the sleep, however, being interrupted at in- 
tervals by wild outcries and writhings, evidently the outcome of abdominal pain, 
although no statement could be obtained from the patient. Again, serous purg- 
ing may be the chief symptom, and arsenical-poisoning has been mistaken for cholera, 
not only during life, but also on the post-mortem table. f 

When arsenical-poisoning is not fatal the convalescence is apt to 
be slow and interrupted by various disorders. Prominent among 
these are affections of the alimentary canal, due to the structural 
changes produced by the poison. Nervous symptoms are common, 
and may affect the motor or sensory sphere separately or together. 
In some cases they have developed very suddenly. We have seen 
anesthesia of the feet as the only symptom; motor paralysis may 
exist alone, but it is usually accompanied by anesthesia, hyper- 
esthesia, loss of temperature-sense, great feeling of coldness, or other 
disorder of sensation, and not rarely excessive pain, which may be 
aching or lancinating. Occasionally there are severe cramps. Normal 
sensibility is usually regained before normal motility. Of one hundred 
cases of arsenical paralysis collected by Imbert-Gourbeyre in more 
than half all the extremities were affected; about one-fourth were 
paraplegic; in the remainder there was hemiplegia or local palsy. 
Most frequently the paralysis was not pronounced above the elbow 
or knee. The lamed muscles are usually sensitive to pressure J and 
undergo rapid atrophy, losing very early their electro-muscular 
contractility, or presenting the "reactions of degeneration." The 
tendency towards more or less complete recovery is remarkable. 
We have seen recovery when the muscular remnants on the wasted 
limbs had for many months been unable to respond to any form of 
electric current; and out of Imbert-Gourbeyre's one hundred cases 
all recovered except three. 

Post-mortem Findings. — The most obvious lesions found after death 
from acute arsenical-poisoning are those of severe gastro-enteritis, 
but often there is also a wide-spread granular or fatty degeneration 
of the tissues. 

The gastric mucous membrane is usually swollen, maculated with patches 
of a deep crimson or more commonly brownish-red color, and is often softened 
and covered with a diphtheritic exudation, but is rarely ulcerated. Perforation is 
exceedingly uncommon. The mucous membrane of the upper part of the small 

* See Imbert-Gourbeyre (Monileur des Hopit., 1857), also A. Huber (Zeitschr. Klin. Med., 1888). 

t See Virchow's Archiv, 1870, 1. 

t Consult C. Gerhard (Sitzungsb. Physik. Med. Gesellsch. Wurzburg, April, 1882), Renner 
(Ueber ein Fall von chron. Arsenvergift., Wurzburg, 1876), W. P. Mcintosh (JV. Y. Med. Record, 
Feb. 1885, 145), Seguin (Journ. Nero, and Ment. Diseases, Oct. 1882, vii. 665), and 0. K. Mills 
(Trans. College of Physicians of Philadelphia, 3d series, vi.; Archives de Physiol. Norm, et Path., 
1884, iv.). 

23 



354 GENERAL REMEDIES 

intestine, and sometimes of the whole of it, is in a condition similar to that of the 
stomach. In some cases the lesions very closely resemble those of cholera, as was 
first pointed out by Virchow. In the microscopic examination of a cadaver whose 
bowels were filled with a "rice-water" fluid, that observer found in the intestinal 
contents epithelial flakes and the fungus described by Klebs as peculiar to and 
indeed, the cause of, cholera. The epithelial cells of the mucous membrane' were 
choked with granules, many of them in an advanced stage of fatty degeneration; 
the interstitial tissue was full of large round granulated cells; the solitary glands 
and Peyer's patches were very much swollen. These facts have been confirmed 
by Hoffmann. The gastro-intestinal lesions produced by arsenic are not due solely 
or largely to its immediate local effect, since they occur equally when the animal 
is killed by injection of the poison into a vein. The local influence of the drug is, 
however, probably not altogether lost, since Unterberger found that a larger dose 
was required to kill an animal by venous injection than by exhibition by the mouth. 
Curious and at present unexplainable anomalies occur in the distribution of the 
gastro-intestinal inflammation, and autopsies have been reported in which the 
stomach lias altogether escaped. 

M. Karajau reports a case which had been mistaken during life for acute at- 
rophy of the liver; Grohl and Mosler one in which they found fatty or granular 
metamorphosis of the glands and epithelium of the stomach or intestines, of the 
cardiac muscle, of the diaphragm, of the cortical portions of the kidney, and, to 
a slight extent, of some of the voluntary muscles; I. I. Pinkham one in winch the 
liver, kidneys, and epithelial lining of the peptic glands were almost destroyed; 
similar lesions have also been reported by M. V. Cornil and by Fereol. 

As was first pointed out by Salkowsky when animals are poisoned by a small 
dose of arsenic, so as to live from three to six days, the liver * becomes much en- 
larged and very fatty. On microscopical examination, the cells on the exterior 
of each acinus are natural; those in the centre in the most advanced stages of de- 
generation. The kidneys are similarly affected, — their tubes choked up with fat- 
globules, their epithelium almost completely destroyed. The muscles of the heart 
and diaphragm are also compromised. 

In frogs poisoned with arsenic the epidermis peels off from the derm, as was 
first noted by Ringer and Murrell, and Emily A. Nunn has found that the influence 
of the poison is first manifested in the under portion of the epidermis, the degener- 
ation progressing from the derm outward. 

In some cases of arsenical-poisoning yellow patches, believed to be due to the 
formation of arsenical sulphides, have been noted on the mucous membrane of the 
stomach and intestines. Similar yellow deposits were found by Chunilal Bose on 
the endocardium. It is probable that in these cases the sulphide is formed after 
death by the aid of putrefactive gases. 

Besides the alimentary lesions, frequently may be found, after 
death from arsenic, evidences of pathological changes in the central 
nervous system. 

N. Popoff found, in dogs killed in a few hours by a dose of arsenic, the spinal 
cord inflamed; after slower poisoning there were masses of "exudate" in the neigh- 
borhood of the blood-vessels, and in very protracted cases the walls of the spinal 
arterioles were found to be thickened and the large cells of the gray matter pro- 
foundly altered. The protoplasm first became opaque and granular; the nuclei 
grew fainter and fainter, and disappeared; vacuoles appeared, and encroached 
more and more on the shrunken body of the cell, which finally melted down. In 

* Salkowsky also noted that early in both arsenical- and antimonial-poisoning the glycogenic 
function of the liver is abolished. Podwyssotsky finds that the first change produced by over- 
whelming doses of arsenic consists in the formation of necrotic foci in the liver (St. Petersburg Med. 
Wochensch., 1888). O. Silverman believes that during life thrombi form in various portions of the 
body (Archiv f. Path. Anat., cxvii). For further discussion see Ziegler (Beilrage Path. Anal., ii.), 
also M. Wolkow (Archiv f. Path. Anat. u. Phys., 1892, cxxvii.). 



ALTERATIVES 355 

the elaborate experiments, however, of C. Alexander upon rabbits, the Bpinal cord 
was found to be healthy, but the nerve-trunks were in a condition of degenerative 
atrophy, and the muscles themselves had undergone changes which were believed 
to be the result of coagulation-necrosis. 

That arsenic is capable, in man, of producing a myelitis especially affecting 
the multipolar cells of the cord is shown l>y the autopsy reported by Erlicki and 
Rybalkin, in which case there was no tenderness of the nerve-trunks. There ap- 
pear to be, therefore, two forms of arsenical paralysis,' one due to myelitic change, 
the other to a wide-spread multiple neuritis, the diagnosis between the two being 
made by the presence or absence of nerve-tenderness, ft is very probable that in 
some cases both lesions are present. In some of these cases trophic changes are 
pronounced: thus, we have seen a growth of hair several inches long cover the 
wasted limbs. If in any ease of arsenical paralysis there were no sensory disturb- 
ance, the probabilities would be very strong that I he lesion was a toxic poliomyelii is. 

We know of no general studies upon the blood of human beings poisoned with 
arsenic. 

S. Betteman has shown that in the rabbit in subacute arsenical-poisoning 
there is a marked lessening in the number of the red blood-corpuscles and in the 
percentage of hemoglobin, without any distinct change in the general percentage 
of leucocytes, although the lymphocytes increase and the eosinophile cells decrease. 
Late in the poisoning nucleated red blood-corpuscles may be found in the circulating 
blood. 

The symptoms of acute arsenical-poisoning resemble so closely 
those of cholera nostras that without the knowledge of the taking 
of the poison, or chemical analysis of the excretions, a positive diag- 
nosis may be impossible. The abdominal pain is, however, usually 
more severe than in the natural disease. 

Death usually results in acute arsenical-poisoning in from eighteen 
hours to three days; but Taylor reports a case in which it occurred 
with tetanic symptoms in twenty minutes, and life has been pro- 
tracted until the sixteenth or even the twentieth day. The effects 
of the arsenical solutions, such as Fowler's, are more rapid and severe 
than are those of the solid drug. Tardicu places the minimum lethal 
dose at from ten to fifteen centigrammes (1.54-2.31 grains). 

W. C. Jackson records a case of recovery, under the early use of emetics, after 
an estimated dose of two ounces had been taken; and E. D. Mackenzie gives an 
account of a man who swallowed an unknown quantity of arsenic in lumps, and 
received no treatment for sixteen hours, yet recovered after passing per anum one 
hundred and five grains of arsenic in two masses. On the other hand, death has 
resulted from the use of very small amounts. Taylor asserts that the smallest fatal 
dose hitherto recorded is two grains. Lachese affirms that six milligrammes (0.09 
grain) will produce decided but not serious symptoms, and that from one to three 
centigrammes (0.154-0.462 grain) are poisonous, and from five to ten centigrammes 
(0.77-1.54 grains) fatal. The escapes from death after the ingestion of large 
amounts of arsenic have, without doubt, depended upon its being, as in the cases 
above narrated, in an insoluble form. 

Treatment. — As arsenic in large doses generally induces vomiting, 
it is rarely necessary in poisoning to evacuate the stomach by arti- 
ficial means. If free emesis, however, have not occurred, a prompt 
emetic, such as mustard or zinc sulphate, should be at once exhibited, 
and very generally the stomach should be well washed out by large 
draughts of warm water, with salt, if necessary for the return of the 



356 GENERAL REMEDIES 

water. With the emetic, or sooner, if possible, the antidote should 
be administered. The most certain antidote is the freshly precipitated 
ferric hydroxide, which forms with arsenous acid a very insoluble 
compound. The antidote must be freshly prepared, and must be 
given in great excess; according to the experiments of T. and H. 
Smith, of Edinburgh, at least eight grains of the iron being required 
for the conversion of one grain of the arsenous acid. 

In practice, any of the official ferric solutions — that of the chloride being gen- 
erally preferred, as most readily procured — should be neutralized by sodium car- 
bonate or preferably by magnesia, and a portion of the precipitate given at once, 
stirred up in hot water. The remainder of the antidote, having been hastily washed 
by emptying it on to a piece of muslin or in a filter, pouring water on it and allowing 
it to drain, should be administered very freely, indeed indefinitely, as it is entirely 
harmless. H. Kohler, of Halle, has made an elaborate series of chemical, physio- 
logical, and clinical experiments upon the comparative antidotal values of the 
saccharated ferric oxide and the freshly precipitated ferric hydroxide. His results 
indicate that the former preparation is the better; but, as the efficiency of the 
hydroxide has been so frequently proved at the bedside, further testimony is desir- 
able before it is superseded, especially since the other ferric preparation is not official 
with us, and is not so readily prepared on the spur of the moment as is its fellow. 
Dialyzed iron has been used with very good results, but it is much better to precipi- 
tate it, just before administration, with a small amount of ammonia or other alkali. 
Magnesia, freshly calcined or freshly precipitated from a solution of its salts, is an 
antidote of some avail in arsenical-poisoning, but is decidedly less efficient than 
the iron oxide. 

The best form of the iron antidote is probably the Ferric Hydroxide 
with Magnesium Oxide (Ferri Hydroxidum cum Magnesii Oxido, 
U. S.), Arsenical Antidote of the German Pharmacopoeia. It is made 
by precipitating the solution of ferric sulphate by magnesia. In 
emergencies, Monsel's solution, tincture of the chloride of iron, or 
any solution of an iron salt, may be substituted for the tersulphate 
solution. 

In arsenical-poisoning castor oil should be administered for the 
purpose of expelling the poison from the bowels, and demulcent 
drinks, opium, stimulants, dry external heat, and rubbing should be 
employed as called for by the symptoms. When there is a tendency 
to suppression of urine, very large draughts of feebly alkaline water 
should be given as frequently as the stomach will bear. 

Chronic arsenical-poisoning is often difficult of diagnosis; the 
symptoms are usually both local and constitutional. When the 
poison has entered the system through the respiratory tract the 
local irritation will be shown by dryness of the throat, coughing, 
and other evidences of chronic bronchitis or severe laryngo-bronchial 
catarrh. When the poison has entered the system through the ali- 
mentary tract, loss of appetite, with frequent vomiting and violent 
diarrhoea, are common. The general symptoms consist of depression 
of spirits, irritability, insomnia, giddiness, failure of memory, some- 
times marked mental failure. According to Reynolds, in the epidemic 
which was caused by arsenical beer, involvement of the nerve- 
trunks was very common. There were in these cases marked disturb- 



ALTER ATI VMS 357 

ances of sensation, paresthesia, and partial anesthesia, although 
complete anesthesia was rare. There may be muscular tremors or 
stiffness; vertigo or other disorders of equilibrium are sometimes 
Been, while violent neuralgic pains, with numbness of the extremi- 
ties, marked tenderness of the nerve-trunks, and other results of 
peripheral neuritis, are not rare. In most cases of chronic arsenical- 
poisoning without a history the congeries of symptoms is, however, 
sufficient only to arouse suspicion and to call for a chemical exami- 
nation of the urine. It should always be remembered that a periph- 
eral neuritis is usually due to the presence of some poison, and that 
a group of wide-spread atypical symptoms not characteristic of any 
distinct disease is usually either toxic or diathetic. 

Sometimes in acute, more frequently in chronic, arsenical-poison- 
ing, or as the result of long-continued medicinal use of the drug, 
certain disorders of the skin appear.* Of these, herpes zoster seems 
to be the most frequent; it probably is the result of an arsenical 
neuritis. Another common skin affection is erythromelalgia, the 
painful red swelling of the epiderm. In protracted cases there is 
frequently thickening of the horny tissue in the palms of the hands 
and soles of the feet, which occasionally extends up the limb. The 
formation of transverse ridges across the nails, the result of the hyper- 
keratosis, has also been noted. The deposit of pigment in the skin 
and mucous membranes is an almost constant symptom, — while 
there have been noted a number of other changes in the skin, such as 
erythematous and desquamatous eruptions, urticaria and subcu- 
taneous oedema, vesicular eruptions, bullae, papules, pustules and 
ulcers, purpura, shedding of the hair and nails, and keratosis. 

In artisans who work in copper local arsenical-poisoning is not 
very rare. Ulcers about the roots of the nails are generally the first 
trouble in these cases, but after a time eczematous or papular erup- 
tions appear, and even subdermal erysipelatous inflammations are 
developed. Very commonly to these local symptoms are added, 
after a time, the usual phenomena of chronic arsenical-poisoning. 

In the arts, preparations of arsenic are largely used as pigments ;f 
and, excepting the manufacturers of arsenical compounds, it is 
almost exclusively those who are accidentally exposed to the 
deleterious influence of these pigments that suffer from chronic 
arsenical-poisoning. 

* See Schmidt's Jahrb., clxv.; Deutsch. Archiv Klin. Med., 1899, xliv.; Boston Med. and Surg. 
Journ., cxviii., cxix., cxx., exxi., exxii.; Ann. de Dermatol, et de Syph., 1897, viii. 4, 345; Monats. 
1. Prakt. Dermatol.. 1897, xxiv. 3, 137. 

t For an excellent report upon this subject, see Report of the State Board of Health of Massa- 
chusetts, Jan. 1872, where it is stated that from five hundred to seven hundred tons of arsenical 
pigment were manufactured in 1802 in England alone. Fatal chronic arsenical-poisoning from 
working in aniline dyes is reported in Sticker's Jahrb., 1877, 501. F. C. ShattucK (Med. News, 
1893, lxii.) reports a number of cases in which the symptoms have been gastro-intestinal irritation, 
anemia, dermatitis, redness of the conjunctiva, puffiness under the eyes, headache, irritation of the 
upper air-passages, albuminuria with casts and blood, and peripheral neuritis. The number of 
cases of chronic arsenical-poisoning detected in and about Boston, contrasted with the rest of the 
world, is something remarkable, and is scarcely to be accounted for by the alleged superior acute- 
ness of the Boston physicians. A further difficulty of the subject is that arsenic has been detected 
in the urine of many normal Bostonians. 



358 GENERAL REMEDIES 

The poisonous colors are of various hues, and, being very cheap, and remark- 
able for their purity of tone and their permanence under exposure to light, are 
much used by paper-makers. Scheele's Green — copper arsenite — contains fifty-five 
per cent., by weight, of arsenous acid; and Schweinfurt Green — the aceto-arsenite 
— fifty-eight per cent. The arsenical dyes are not all green, but may be in almost 
any hue; they are largely due to the use of arsenic in the manufacture of magenta 
and other aniline colors. E. S. Wood, of Harvard, has shown that in different 
parcels of the same goods one will contain arsenic and the other not, because the 
aniline dyes are sometimes contaminated with arsenic and are sometimes free from 
it. These poisonous colors are by no means confined to wall-paper. Sweetmeats 
have been colored with them; pasteboard boxes, artificial flowers, tarlatan dresses, 
India muslins, cretonnes, walls of dwellings, shelves of groceries, toys of children, 
and various other articles have been made the vehicle of death, so that hundreds 
of cases of poisoning have resulted from the use of these pigments, which ought to 
be banished by the strictest laws. In most cases it is probably the minute dust, 
which is separated mechanically and diffused through the room, that produces the 
fatal result; but poisoning lias occurred when the arsenical paper was covered over 
with another paper. Hambers has made elaborate chemical researches upon the 
air of these apartments, and believes that he lias demonstrated that some arsenic 
escapes in the form of arseniuretted hydrogen. Not rarely the poison has been 
taken directly into the stomach, especially by children. 

The chief indications in chronic arsenical-poisoning are to remove 
the patient from the exposure and to treat symptoms as they arise. 

Post-mortem Imbibition. — Owing to the extensive use of embalming with liquids 
made either directly from arsenical preparations or from commercial chemicals 
which habitually contain arsenic as an impurity, it is becoming extremely difficult 
in criminal legal practice, as it occurs in the United States, to prove death from 
arsenical-poisoning. Although the subject is somewhat aside from the main motif 
of the present volume, its importance seems to require a brief authoritative con- 
sideration, the details of which may be found in recent works on toxicology. The 
old belief that the finding of arsenic in the brain or organs distant from the abdo- 
men was proof that the poison had been administered during life, and had been 
scattered by absorption * and not by imbibition, is absolutely incorrect. 

The qualitative distribution of arsenic in the body is of very little service in 
most cases in determining the question as to whether the poison has been given 
before or after death. Arsenic which lias been injected into the thorax or into the 
abdomen, after death, may be found subsequently in the brain and other distant 
parts of the body. More respect should be given to the quantitative distribution of 
arsenic. It is naturally to be expected that more arsenic should be found in the 
parts adjacent to the points of injection than in distant portions of the body; and 
that the position of the body, through the force of gravity, should influence the 
distribution of the poison. Thus, if the corpse has lain upon the back more arsenic 
should be found in the back tissues than in those in the upper portions of the body; 
if on the left side more poison should be found in the left than in the right kidney. 
Nevertheless, when a body has lain for many weeks after post-mortem arsenicaliza- 
tion the laws of diffusion assert themselves against the law of gravity. 

To be of any value whatever the quantitative chemical study of the different 
organs must have been made with the greatest care and attention to details, not 
only chemical but also physical. The w T hole organ must have been used or reduced 
to a common pulp, a portion of which has been analyzed. Moreover, the quantita- 
tive differences must be most pronounced or, as it has been well stated by Mann, 
"must be absolute not relative; the left kidney must contain arsenic and the right 
none; it is not enough that the right kidney shall contain less than the left; such a 
difference is compatible with vital absorption." 



poison 



In this paragraph the word "absorption" is used technically to indicate the taking up of the 
during life; " imbibition " to indicate the passage of the poison from tissue to tissue after death. 



ALTERATIVES 



359 



l'\ivpt under rare circumstances, as when the body has been buried only a few 
days after embalming, bo thai there has not been time for the processes of imbi- 
bition to carry the poison throughout the Organs, the expert is not justified in assert- 
ing from quantitative evidence that (lie poison has been taken during life; (lie im- 
perilling of life by overconfidence of statement is not a rare crime in American 
courts. To-day is as true as ever the dictum of Wittliaus and of Torscllini, that, 
it is impossible in most eases to distinguish with positiveness by chemical analysis 
between absorption and imbibition, or, in other words, whether the poison has been 
put into the body before or after death.* 

Administration. — The beginning dose of arsenic is one-thirtieth 
of a grain (0.002 Gm.), which should be given in pill after meals, and 
be slowly increased until a perceptible influence, or the desired thera- 
peutic effect, is obtained. In many cases {chorea, lymphoma, inter- 
mittent fevers, etc.) it is necessary to push the remedy until decided 
evidences of poisoning are secured: in this case a liquid preparation 
should be selected. 

Cacodylic Acid. — Cacodylic acid is chemically di-methyl-arsenic acid. Several 
of its salts have been employed in medicine as substitutes for arsenic. It has been 
claimed for these preparations that they are much less poisonous than the ordinary 
arsenical preparations, and can be used freely without danger of causing unpleasant 
symptoms. It would seem that their low degree of toxicity depends upon the 
fact that the arsenic is so firmly bound up in the composition that it is liberated 
in the body only in very small quantities, since the experiments of Heffter indicate 
that only about two or three per cent, of sodium cacodylate is destroyed in the 
body and eliminated as arsenic. It is therefore probable, as claimed by Heffter, 
that the cacodylate is not active as such but only through the liberation of free 
arsenic. This view is also held by Fraser, who has used the remedy in a number 
of cases of chorea, eczema, leukemia, and chlorosis without special result. The remedy 
has been especially lauded by Gautier, who has employed it in various forms of 
tuberculosis with asserted good results. Sodium cacodylate has been used as a 
substitute for arsenic in all the conditions in which this remedy is useful, in doses 
of one-quarter to one grain (0.016-0.06 Gm.). In chlorosis and other forms of 
anemia the cacodylate of iron is preferred, and may be given in the same dose. 
According to Gautier it is always preferable to give the remedy subcutaneously. 
Under these circumstances a five-per-cent. solution may be employed, of which 
15 minims (1 C.c.) may be given at a dose. 

Atoxtl. Meta-arsenic-anilid. — This is a white, odorless powder, soluble in 
twenty per cent, of hot water, and containing thirty-seven and six-tenths per cent, 
of metallic arsenic. According to Blumenthal it is forty times less poisonous than 
arsenic acid, but as its physiological, toxic, and remedial properties are probably 
in direct proportion to the amount of arsenic eliminated in the system, it does not 
seem probable that it has any advantage over the older preparations of arsenic. 
It is claimed, however, to lend itself especially well to hypodermic medication; 
according to Schild, three to fifteen minims of the twenty-per-cent. solution may be 
given hypodermically for five days, subsequently on alternate days. Schild believes 
that it is especially liable to act upon the heart, and considers cardiac weakness a 
contraindication to its use. 

MERCURY. 

Metallic mercury in its ordinary form is almost incapable of absorp- 
tion, but when finely subdivided by trituration with inert substances 

* American readers see especially Medical Jurisprudence and Forensic Medicine and Toxicol- 
ogy, by Witthaus and Becker. Also Text-book of Legal Medicine and Toxicology, by Peterson and 
Haines. Also Forensic Medicine and Toxicology, by Dixon Mann. 



360 GENERAL REMEDIES 

it becomes capable of penetrating the mucous membranes. Prepara- 
tions containing metallic mercury which are recognized by the U. S. 
Pharmacopoeia are: the mass, the ointment, and mercury with chalk. 
Mercury is capable of acting either as a univalent or as a divalent 
base, consequently it forms two series of salts, the mercurous and the 
mercuric. The Pharmacopoeia recognizes of the salts of mercury, — 
two chlorides, two iodides, two forms of the oxide, an oleate, and a 
complex body resulting from the precipitation of solution of 
corrosive sublimate by ammonia known as ammoniated mercury. 

Mercurous chloride or calomel (hydrargyri chloridum mite), occurs 
as a white crystalline powder, insoluble in water, alcohol or ether. 
Mercuric chloride or bichloride of mercury, more commonly known as 
corrosive sublimate (hydrargyri chloridum corrosivum), is in colorless 
crystals, soluble in thirteen parts of water and three parts of alcohol, 
odorless, but with an acrid metallic taste 

Mercurous iodide, or yellow iodide of mercury, is a bright yellow 
amorphous powder without odor or taste, practically insoluble in 
either water or alcohol. Mercuric iodide, or red iodide of mercury, 
is a bright-red, odorless, and tasteless powder, sparingly soluble in 
alcohol and practically insoluble in water; solutions of potassium 
iodide, however, dissolve it easily. 

Two forms of the oxide of mercury are recognized, the yellow and 
the red. In their chemical relations these two preparations do not 
differ. They are both insoluble in alcohol and in water. The yellow is 
amorphous and of a light orange yellow color. The red oxide is com- 
posed of orange-red crystals which become yellow when finely triturated. 

Ammoniated mercury is made by precipitating the bichloride 
with ammonia water and has the formula HgNH 2 Cl. It occurs in 
the form of a white, amorphous powder, with a metallic taste, insoluble 
in water or alcohol. 

Official Preparations : 

Hydrargyrum Not used internally. 

Hydrargyrum Ammoniatum .... Not used internally. 
Hydrargyrum cum Creta [Gray 

Powder] 2 to 10 grains (0.13-0.6 Gm.). 

Hydrargyri Chloridum Mite 

rp . . f Alterative £ to 1 grain (0.03-0.06 Gm.). 

LOalomelJ j Cathartic 2 to 10 grains (0.13-0.6 Gm.). 

Hydrargyri Chloridum Corrosi- 
vum [Corrosive Sublimate] ^ to J grain (1-8 Milligm.). 

Hydrargyri Iodidum Flavum 

[Protiodide] J to 1 grain (0.01-0.06 Gm.). 

Hydrargyri Iodidum Rubrum 

[Biniodide] ^ to | grain (1-8 Milligm.). 

Hydrargyri Oxidum Flavum Not used internally. 

Hydrargyri Oxidum Rubrum. . . . Not used internally. 

Massa Hydrargyri [Blue Mass] . . 1 to 10 grains (0.06-0.6 Gm.). 

Unguentum Hydrargyri [Blue 

Ointment] (50 per cent.) Externally only. 

Unguentum Hydrargyri Dilutum 

(33 per cent.) Externally only. ♦ 



ALTERATIVES 361 

Oleatum Bydrargyri Externally only. 

I'nguentuin llvdiargyri Amnio- 

niati (10 per cent.) Externally only 

Onguentum Bydrargyri Nitratis 

(7 per cenl .) Externally only 

Unguent inn Ilydrargyri Oxidi 

Flavi (10 per cent.) Externally only 

Onguentum Bydrargyri Oxidi 

Rubri (10 per cent .) Externally only 

Emplastrum Hydrargyri (30 

per cent.) Externally only 

Pilula? Catharticse Compositae. ... 1 to 2 pills. 

Local Action. — The local effect of mercurial preparations varies 
from complete inertness to an active escharotic influence, so that 
each preparation must in this regard be studied by itself. 

Absorption and Elimination. — All the official preparations of mer- 
cury yield themselves or the mercury in them to absorption, and after 
absorption to elimination. The metal has been found in the blood,* 
in the urine, in the serum of blisters, in the saliva, in the feces, in the 
pus from ulcers, in the seminal fluid, in the milk of nursing women, — 
indeed, in every conceivable secretion and in every tissue. Heller 
found it in the aborted foetuses of salivated women, and Mayencon 
and Bergeret in the urine of a baby whose nurse was taking calomel; 
and each of these observations has been confirmed by Wellander. 

An enormous amount of work has been done to determine how 
rapidly mercury is eliminated, and whether when given internally it 
is all thrown out of the system. The result of all this labor seems to us 
to prove that the single dose of mercury does not remain in the 
system, but that when the drug is administered constantly for a 
length of time elimination does not keep pace with absorption, so 
that the mercury accumulates in the tissues. Moreover, the elimina- 
tion takes place irregularly and intermittently, for reasons that at 
present cannot be made out. Further, there does not appear to be 
any limit of time during which stored-up mercury may remain in 
the body; indeed, all the evidence points to the possibility of mercury 
being deposited in the tissues in such form that it is practically inert 
and has no influence upon the system; liable, however, under certain 
agencies, to be set free and to exert its power upon the general nutrition. 

There has been much speculation as to the exact form in which mercury is 
absorbed. The only official salt which is at all readily soluble in water is the corro- 
sive sublimate. It is certainly not absorbed as mercuric chloride as it is so power- 
ful a precipitant of albumin that it cannot exist in the system unchanged. Jeannel 
has found that calomel in the presence of an alkaline carbonate lias decomposed 
and a gray oxide was formed. This gray oxide is very sparingly soluble in water 
but if a fatty oil be mixed with the alkaline solution a large part of the mercury is 
dissolved. No plausible explanation of the absorption of mercury is found in the 
solubility of the albuminate of mercury in the presence of the excess of albumin. 

*Gmelin (Bull, de Therap., xiii.); Salkowsky ( Virchow's Archiv, xxxvii. 347); Mayencon and 
Bergeret (Robin's Journal de I A natomie, 1873); Klinik (Detroit Med. Joum., May, 1877). 



362 GENERAL REMEDIES 

The theory of Mialhe that calomel is converted by hydrochloric acid in the 
stomach into a bichloride and as such absorbed is certainly untrue, for it has been 
shown that the gastric juice at least at the body temperature is not capable of 
forming corrosive sublimate with calomel, and if it were, corrosive sublimate, as 
we have seen, is incapable of being absorbed unchanged. The superstition against 
the administration of acid drjnks, as lemonade, in conjunction with calomel, has 
no chemical foundation. 

The rate of absorption of, mercury is of course affected by the choice of prepara- 
tion and by the method of administration. Wellander has found mercury in the 
urine fourteen hours after its application to the human skin and one hour after its 
subcutaneous administration. Mayencon and Bergeret found that when one centi- 
gramme of corrosive sublimate was given hypodermically to a dog, the urine for the 
next twenty-four hours contained mercury, afterwards none. When a centigramme 
was given daily for ten or twelve days, the urine contained mercury for four or 
five days after the cessation of medication. In their last series of experiments, 
rabbits received the drug, and were killed at different intervals: in half an hour the 
metal could be found in all the tissues, the liver and kidneys containing most of 
it; in four days, or even in a shorter time, mercury given in a single dose was all 
eliminated, and could not be found in the tissues.* 

The evidence in favor of the storing up of mercury in the system is overwhelm- 
ing. In 1880 Vajda and Paschkis stated that they found the metal in the urine in 
different cases, six months, one year, two years, and even twelve and thirteen 
years after the mercurial course. Mayengon and Bergeret found that the exhibition 
of potassium iodide forty-eight hours after the cessation of a mercurial course, 
when the urine was free from mercury, would bring about the immediate elimi- 
nation of mercury. Apparently, using all precaution and having the patient 
carefully watched, H. Stein has obtained weighable amounts of eliminated 
quicksilver from the urine four weeks after its inunction. Schuster has found it 
in the feces three months after the cessation of a mercurial course; indeed, he be- 
lieves that it is thrown off more freely and constantly by the intestines than by the 
kidneys. He also asserts that elimination is completed six months after the cessa- 
tion of an ordinary mercurial course. According to Gola when the kidney elimina- 
tion is great the intestinal output is small and vice versa. In an elaborate memoir 
on the elimination of mercury, Balzer and Klumpke state that extraordinary exac- 
erbations and remissions occur in the elimination during treatment, that Michael- 
owsky and Souchow have shown that the effect of potassium iodide is small, but that 
Stepanow has proved that the hot-air baths increase enormously the elimination. 
It appears to be established by Stein, that in these cases of long continuance the 
mercury escapes not only through the kidneys, but is also excreted by the salivary 
glands as well as by the intestines, and hence its continuing elimination may be 
overlooked by the chemist, who simply studies the urine. 

Physiological Action. — After absorption, all of the preparations 
of mercury appear to affect the system very similarly. When a mild, 
unirritating, preparation is introduced into the system so as to produce 
constitutional effects, the first symptoms of its action are to be looked 
for in the mouth. In the mildest degree these symptoms consist of 
a slight fetor of the breath, and some soreness of the teeth when 
knocked forcibly together or struck with a key. Mercurial fetor of 
the breath is generally the first indication that the drug is affecting 
the system, and is sooner or later accompanied by a disagreeable 
metallic taste. If the use of the mercury be persisted in the gums 

* Method of Preparing Tissues for Microscopic Detection of Mercury. — J. Almkvist (S. J., Bd. 
eclxxx., p. 177) soaks the freshly cut pieces for eight or ten hours in a solution of sulphuretted 
hydrogen, containing four per cent, of nitric acid, producing a yellow precipitate of mercuric 
sulphide; subsequently he hardens in alcohol or other fluid not containing iodine, and cuts. 



ALTERATIVES 3G3 

become swollen, soft, and spongy, bleeding on very slight abrasion, 
and there is a decided increase in the secretion of saliva. Beyond this 
point the therapeutist is never justified in carrying the use of the drug. 
If it be done, the local symptoms in the mouth increase in severity, 
the tumefied gums become inflamed, very vascular, and marked by 
a dark red line at the junction of the teeth; the tongue is also swollen, 
sometimes enormously, protruding from the mouth, whose closure it 
may entirely prevent; the teeth are loosened in their sockets; the 
saliva is enormously increased in quantity and altered in quality, 
forming great, ropy, viscid masses, which pour over the thickened lips; 
the parotid glands, and even the submaxillary, are very much enlarged 
and tender. Severe ptyalism may be accompanied by marked fever, 
and nephritis is a not uncommon occurrence. Loss of the teeth, 
extensive ulceration of the soft parts, and even necrosis of the jaw- 
bones have occurred, and death from exhaustion resulted, or the 
patient struggled through to recovery, seamed and disfigured for life. 
In these cases passive hemorrhages often recur again and again, and 
may contribute largely to a fatal result. During severe ptyalism 
emaciation goes on rapidly, and seems to especially affect imperfectly 
organized tissues, so that exudations very generally rapidly disappear. 
The disturbance of nutrition is further shown in some cases by the 
occurrence of ulcers upon the extremities. The blood suffers very 
decidedly, becoming more fluid and watery than normal and having 
its power of coagulation impaired. According to the researches of 
Wright, its solid constituents are notably diminished, including 
albumin, fibrin, and the red corpuscles, and it contains a large quantity 
of fetid, fatty material. These observations of Wright have been 
confirmed upon animals by Wilbouchewitch, and by I. Hughes 
Bennett. 

Although large doses of mercury lower the general nutrition and 
destroy the crasis of the blood, it is probable that when given in very 
minute doses it has tonic properties. 

In 1869 Liegeois asserted that the subcutaneous injection of very minute doses 
of quicksilver produces in healthy men an increase of their bodily weight, and in 
1876, in two experiments, E. L. Keyes found that not only was the bodily weight 
increased, but, as determined by actual count, the number of the red corpuscles 
was decidedly augmented. Hermann Schlesinger has laboriously experimented 
upon rabbits and dogs. All other conditions being similar, those rabbits which 
received the mercury increased in weight a little more than did those to which 
mercury was not given, but the augmentation of the red blood-disks was distinctly 
greater in the mercurialized animals. With dogs the results were more decided, 
both bodily weight and blood-corpuscles increasing much faster in the animals to 
which mercury was given. I. Hughes Bennett had previously obtained results 
similar to those quoted, and Schlesinger thinks that it must be considered proved 
that very minute continuous doses of mercurials tend in the normal animal or man 
to increase distinctly the weight of the body and the richness of the blood, but that 
it is scarcely proper to call them tonic, as in his belief they act by hindering oxi- 
dation and restricting waste, and not by aiding in reconstruction, — a conclusion 
which is purely theoretic and unproved. In some cases of syphilitic anemia the 
effect of mercury in increasing the number of red blood-corpuscles is very marked. 



364 GENERAL REMEDIES 

This effect is, however, to be attributed to the antisyphilitic influence of the remedy 
rather than to any specific action on the blood-making organs. (For elaborate 
paper, see L. Gaihard.) 

The ordinary symptoms of mercurialization have been sufficiently 
described, but there are on record various anomalous cases. In some 
instances the chief symptoms of mercurialism have been cutaneous. 

The usual eruption is a polymorphic erythema, resembling more or less that of 
scarlet fever. In rarer cases the eruption may be distinctly erysipelatous, with sub- 
dermal cedematous swelling. Sometimes it takes the form of urticaria, or even of a 
roseola; a very severe eczema, becoming finally pustular, has in some cases been 
produced, most frequently as the result of an inunction; while mercurial pemphigus 
and purpura have both been recorded. Usually the eruption is fugacious, being 
followed in two or three days by more or less desquamation, but very grave cases 
have been recorded in which there has been a universal dermatitis, with great 
swelling of the face and extremities, excessive desquamation, followed by thicken- 
ing and infiltration of the subdermal tissues, excoriation, violent fever, disturbance 
of the respiration, and death; or, if the patient survive, months of illness (see M. A. 
Morel-La vallee) , 

Sometimes the influence of mercury falls almost exclusively upon the 
nervous system, and produces a peculiar train of paralytic phenomena. 

Nervous mercurialism occurs chiefly when mercurial vapors find entrance 
through the lungs, and is most frequently seen in workers in the metal. It is gen- 
erally the result of long exposure; but that it may be produced in a very short time 
is proved by the case, related by Christison, of two barometer-makers who slept one 
night in a room containing a pot of mercury upon a stove. One was severely sali- 
vated, the other was affected with a shaking palsy which lasted all his life. Accord- 
ing to Sigmond, the attack of mercurial palsy, which is sometimes sudden, some- 
times gradual, begins with unsteadiness and shaking of the extremities and of the 
muscles of the face, which movements interfere with walking, speaking, or chewing; 
the tremors become frequent, nay, almost constant; "every action is performed by 
starts." If the exposure be continued, sleeplessness, loss of memory, and death 
terminate the scene. A peculiar brownish hue of the whole body, and dry skin, 
generally accompany the disease. In its first attack it may be mistaken for St. 
Vitus's dance; in its latter stages, for delirium tremens. According to Noel Gueneau 
de Mussy, these two forms are distinct varieties rather than different stages of 
mercurial tremors. In the" latter the affection simulates paralysis agitans in its 
shaking movements; in the former the motions are violent, and occur independently 
of the will of the patient, even when he is lying quietly in bed. In a case reported 
by L. Langer, the electro-contractility of the affected muscles was much heightened. 

Paralysis from chronic mercurial-poisoning is said to be not a rare affection 
among artisans and miners who are in their daily occupation exposed to contact 
with the metal or its fumes. The subject has been thoroughly discussed by M. M. 
Letulle, to whose paper the reader is referred for a collection of recorded cases 
and for details. In a case reported by Sigmond, symptoms similar to those of 
chronic lead-poisoning, including wrist-drop, followed repeated mercurial inunc- 
tions. In some cases mercurial paralysis takes the form of multiple palsy, or of 
a brachial or crural monoplegia, or of an obscure local palsy, as in a case reported 
by Kussmaul, in which there was aphonia from paralysis of the laryngeal muscles. 
Almost invariably the loss of motor power is accompanied by an anesthesia, which 
may be wide-spread or may be in isolated islets, or may take the form of hemi- 
anesthesia. The loss of sensation is very rarely absolute; simple loss of the thermic 
sensibility or analgesia may exist alone. Partial anosmia or amblyopia may show 
that the nerves of special sensation are affected. Neuralgic pains may be the per- 
manent result of a mercurial exposure, and epilepsy and even insanity, most fre- 



ALTE11AT1YKS 



305 



quently of the melancholic type, are stated to bave been so produced. According 

to Letulle, trophic changes are not common, the paralyzed inuscles not, Undergoing 
atrophy, and retaining their normal relations to the galvanic and faradic currents. 
When the thighs are affected the knee-jerk may entirely disappear, (iuinon 
describes violent hysteria following upon chronic mercurial-intoxication. 

In some cases exposure to the vapor of mercury, or even its per- 
sistent medicinal use, has resulted in the production of a state of the 
system somewhat resembling scurvy, characterized by great anemia, 
emaciation, and general loss of power, with loss of the hair, aching 
pains in the bones and joints, oedema, fetid breath, diarrhoea, and 
generally disordered secretions. This is the so-called mercurial 
cachexia* 

There is some reason for believing that the pancreas is especially 
affected by mercury. Thus, in a case related by Copland, a woman 
after excessive salivation experienced deep-seated epigastric pain 
and heat, with nausea, thirst, and fever, and voided thin stools 
containing liquid resembling salivary fluid. At the postmortem the 
pancreas was found weighing four ounces, red, congested, and with 
its duct dilated. 

The experiments of I. Brauer and of V. Tirelli show that in the lower animals 
very large doses of mercurials have a powerful depressing influence upon the central 
nervous system, and may produce death by respiratory paralysis; that when smaller 
doses are given a condition of nervous excitement is produced, with increase of 
the tendon-reflexes, followed by partial paralysis and ataxia; and that in chronic 
poisoning by very small doses continuously administered a degeneration of the 
nervous system takes place, probably beginning in the anterior motor cells of the 
spinal cord. This degeneration appears, however, not to be characteristic of the 
mercurial poisoning, but to be similar to that produced by phosphorus, arsenic, 
and various other poisons. 

Little attention has been paid to local mercurial poisoning, but A. 
W. Foot has reported the production of paralysis of the muscles of 
the hand and forearm by contact with the red mercury iodide during 
the rubbing of cattle with a salve containing it. It is asserted that 
in some peculiar persons the external, and even the internal, use of 
small amounts of mercurials will produce violent eczema or other 
skin-eruptions (Alexander). 

The constitutional action of mercury shows that it has relations 
to the nutrition of the whole body. The alterations in the blood, the 
wasting, the perverted functions of nerves and of glandular tissues, 
the various skin eruptions, all point to a profound influence upon the 
whole organism. After death from such irritant preparations of 
mercury as corrosive sublimate, violent diphtheritic colitis is the 
ordinary lesion, and, as was first shown by Salkowsky, structural 
alterations abound in the kidneys, accompanied by a peculiar deposit 
of calcium phosphate: that the renal lesions may be produced by the 
non-irritant preparations of mercury has been shown by B. Silva, 



* For an interesting paper in regard to mercurialism in looking-glass makers, see article by 
Wollner {Munch. Med. Wochen., July, 1892). 



366 GENERAL REMEDIES 

who has found true desquamative nephritis in dogs to which calomel 
had been given. Felix Klemperer discusses the literature of the subject 
fully, and concludes that the successive changes in the kidneys are: 
excessive hyperemia, parenchymatous nephritis, hemorrhagic ne- 
phritis, with wide-spread degeneration of the epithelium, and in about 
one-half of the cases deposits of chalky material. Virchow states 
that the coexistence of distinct renal chalky deposits with diph- 
theritic hemorrhagic colitis justifies the diagnosis of corrosive subli- 
mate poisoning, but Klemperer affirms that this condition can be 
produced by bismuth and some other poisons. The later researches of 
E. Lentert led to a similar conclusion, — namely, that the calcification 
of the kidneys makes the diagnosis of corrosive sublimate poisoning 
very probable but not assured. The calcification of the kidneys, 
which is often accompanied by true calcareous deposit in the 
tubules, and which may be sufficient to cause the kidney structure 
to cry out under the scalpel, was attributed by Prevost to the decal- 
cification of the bones; a theory which seems to have been disproved 
by Klemperer (confirmed by Paul Binet). 

According to our present evidence, it does not seem probable that 
mercury increases the nitrogenous waste. It is true that Hermann 
von Boeck, in a case of mercurialization in a man, found that there 
was a very slight increase in the elimination of nitrogen during the 
mercurial periods, but H. Schroder, and Guttenberg and A. Gurber, 
in experiments made upon rabbits, obtained an absolute decrease in 
nitrogenous elimination during mercurial poisonings. 

Therapeutics. — The use of mercury in affections of the liver and 
of the alimentary canal is fully discussed in another portion of this 
treatise; and, although the drug has been used for almost innumer- 
able purposes in times past, it seems here only necessary to speak 
of its action as an antiphlogistic and as an antisyphilitic. 

Antiphlogistic Action. — The use of mercury in inflammation origi- 
nated towards the close of the eighteenth century with Robert Hamil- 
ton, and soon became universal in England and America. It is a matter 
of regret that no sufficient analyses of the blood of pt3 r alized persons 
have been made to determine exactly what are the changes produced 
in the vital fluid by mercury. The indications are, however, very 
strong that chief among them is a lessening of the amount of fibrin. 
As is well known, increase of the hemic fibrin is one of the most 
characteristic effects of inflammation: consequently, theory, instead 
of being opposed to the antiphlogistic use of calomel, affords at least 
some grounds for the belief that there is more or less antagonism 
between the processes of mercurialization and of inflammation. 

All important evidence as to the antiphlogistic value of mercurials 
at present available is clinical, and even of this it seems impossible 
to find much that is very exact and of such nature as to exclude 
possible fallacies. It is the enormous mass of testimony that over- 
rides the probability of fallacy. It is the general judgment of the 
profession, founded upon the thousand daily observed bedside facts, 



ALTERATIVES 367 

that endorses the use of mercury as an antiphlogistic. In other words, 
our knowledge of the value of mercurials in inflammation at present 
is clinical rather than experimental, empirical rather than scientific, 
but it seems scarcely possible that it is not correct. There is one 
inflammatory affection — iritis — which, from its anatomical relations, 
is completely visible al all stages; and the effects of the drug upon its 
processes have been noted from day to day hundreds of times. Ocu- 
lists are, we believe, agreed that when there is a marked tendency 
towards the exudation of lymph in this disease, mercury should be 
exhibited until ptyalism is induced. 

Of all inflammations, those of the serous membranes seem to be most 
allied to iritis; and it is exactly in the condition above spoken of, 
where there is a tendency to fibrinous exudations in pleuritis, peri- 
tonitis, and pericarditis, that mercury is so constantly employed with 
so good an effect. In parenchymatous inflammations, especially in 
pneumonia and in hepatitis, mercury has been used with asserted 
advantage by many practitioners, but its value is certainly more 
questionable than in serous inflammations. In pseudo-membranous 
angina or laryngitis, and in true diphtheria, the mercurials are very 
useful remedies; they should be given in small repeated doses, prefera- 
bly in the form of dry calomel powders, it being probable that the 
good effect is at least in part due to the diffusion of the mercurial 
over the diseased surface and the consequent antiseptic influence. 
There is much doubt as to the exact advantageousness of mercurials in 
endocarditis; but, as it is extremely important, if possible, in that dis- 
ease, to prevent exudation, and as mercury is the most efficient known 
agent for effecting this, it should be administered freely and at once. 

In whatever disease a mercurial is administered as an antiphlogis- 
tic, it should be given during the stage of exudation, and to facilitate 
the absorption of the newly organized lymph after it has ceased to be 
thrown out. In the majority of cases mercury given for its constitu- 
tional effects should be combined with opium, to prevent its acting 
on the bowels. 

Calomel should not be used in adynamic inflammations, or where 
the exudation is serous rather than fibrinous. In puerperal peritonitis 
it has been strongly advocated by some and as strongly condemned 
by others, simply because there are two varieties of the disease, the 
sporadic or sthenic, and the epidemic or asthenic; and in the one both 
bleeding and calomel are strongly indicated, while in the other they 
are effective only for evil. 

Mercury as an Antisyphilitic. — The literature concerning the use 
of mercury in the treatment of syphilis is so enormous as almost to 
defy analysis; through the discussion, however, has finally been 
reached practical unanimity of professional opinion, the only points 
of difference being as to details of "how" and "when" the mercury 
should be employed. 

Whenever a venereal ulcer offers the characteristics of a true 
chancre, mercury should be exhibited. Many practitioners believe 



368 GENERAL REMEDIES 

that it is wiser for diagnostic purposes, in all cases of doubt as to the 
character of the primary sore, to withhold the mercury until secondary 
manifestations appear. Under any circumstances, so soon as the 
diagnosis of syphilis is clearly established, mercury should be employed 
in some form or other. Our own practice is in the beginning of the 
treatment to push the mercury to the point of mild ptyalism, — i.e., 
to the production of slight evidences of constitutional drug action, — 
and then to continue the medicine persistently in small doses for at 
least eighteen months, increasing the dose up to mild ptyalism if at 
any time there should be a recrudescence of the symptoms. 

In tertiary syphilis mercury is to be used cautiously. It is not, 
however, the mere length of time that has elapsed since the infection, 
but the condition of the patient, that guides the judicious practitioner. 
So long as there is no decided cachexia, if the patient has not recently 
been through a mercurial course, mercury should be freely used when 
the local lesion threatens to kill directly or to produce organic changes 
in a vital organ. Thus, a gumma in the heart-wall, in the upper 
spinal cord, or in some vital brain-region may imperatively demand 
active mercurialization. We have twice seen a patient slowly recover- 
ing from brain-syphilis under the influence of the iodides die by the 
accident of an epileptic arrest of respiration. In these cases the more 
rapid resolution of the gummatous masses by mercury, had that drug 
been exhibited, would in all probability have prevented the fatal fit. 
In hereditary syphilis a prompt mercurial impression offers the best 
chance of relief. At any stage of syphilis some caution and judgment 
should be used in the administration of mercury. As was shown by 
Keyes, the small dose of mercury in infected patients frequently acts 
distinctly in increasing the number of red blood-disks. Wilbouche- 
witch found that the mercurial when first exhibited increased the 
number of red blood-corpuscles in syphilitic patients, but after a 
time appeared to produce anemia. Whatever preparation be employed 
it should be so administered as to cause only signs of the constitutional 
action in the mouth. It is never necessary to ptyalize the patient 
severely. There are various methods by which this may be done. 
That most frequently employed, because most convenient, is the 
administration of small doses of calomel or blue pill by the mouth: 
from one-fourth to one-half grain of calomel, or twice as much of the 
blue mass, combined, if necessary, with opium, to prevent its action 
upon the bowels, may be given three times a day, and increased if 
required. Instead of the internal use of the mercurial, the system 
may be brought under its influence by inunctions. 

In practising inunctions it is essential to remember that when 
mercury is applied to a hairy surface it is very prone to cause a trouble- 
some irritation, due to inflammation about the hair-follicles. Indeed, 
the continuous application of the mercurial to almost any surface of 
the body will cause finally an eczematous eruption. Further,, when 
the skin is in thoroughly good condition it absorbs much better than 
when it is irritated. The frequent use of the hot baths seems also 



ALTERATIVES 369 

to aid in the absorption, ami possibly also in the elimination of the 
mercury; and the good effects obtained at the Arkansas and other 
thermal springs largely depend upon the frequent employment of 
the hot bath with the tree use of the mercurial. It is therefore usually 
bettor to have the inunction practised in the evening, after the patient 
has had a prolonged bath; and in cases of great urgency the baths 
may be repeated two or three times a day, so as to produce free sweat- 
ing, and the inunction practised, it may be, twice a day. In order to 
avoid irritation of the skin, a regular order should be maintained in 
the application, as follows: first day, inner side of both upper arms; 
ueond day, inner side of both thighs; third day, inner side of both 
forearms; fourth day, inner side of both legs; fifth day, upon both 
groins; sixth day, upon the back; seventh day, recommence the series. 

The advantage of inunction is that the digestion is less likely to 
be disturbed than when the drug is exhibited by the mouth;* the 
disadvantages are the greater or less publicity which it entails, the 
trouble which it involves, and its apparent dirtiness. In private 
practice it is rarely practised except in the case of infants, when the 
mercurial ointment is rubbed into the abdomen and armpits, or often 
simply smeared upon the flannel roller or binder which usually en- 
velops the body. The mercurialization of the nurse, with the object 
of affecting the child, is unjustifiable, unless the nurse and the nursling 
are alike diseased: indeed, to allow a syphilitic child to feed at the 
breast of a healthy woman is a crime. 

Mercury may be used hypodermically, often with great advantage, 
in the treatment of syphilis. The search after novelties by clinicians 
and chemists has led to the invention of very many new preparations 
and the production of a very large literature, which was summarized 
in previous editions of this work, and is discussed in great detail in 
current monographs on syphilis. As the result of much experience, 
however, we are confident that the whole matter can be summed up 
in a single sentence, — namely, that no mercurial preparation has any 
distinct advantage over corrosive sublimate for hypodermic adminis- 
tration; and that the great mass of the proposed preparations, includ- 
ing all those which contain calomel, are much more dangerous than 
is the corrosive chloride. From one-sixteenth to one-eighth of a 
grain of the bichloride should be injected deeply into the muscles of 
the back or of the thigh daily or every other day, according to the 
needs of the case; care being exercised to see that the part is well 
rubbed immediately after the injection, so as to dispel the local 
accumulation of fluid, and that injections are not given on successive 
days in places near to one another. In some cases very pronounced 

• The action of inunctions is usually very mild and tractable, but Von Sackur (Berl. Klin. 
H'orhrntch., 1892, xxix.) has reported a case of death in six days, preceded by symptoms of violent 
irritation of the stomach, the intestines, and the kidneys, with furious gangrenous ptyalism, appar- 
ently produced by a single inunction with mercurial ointment. Ludwig, of Vienna, in an examina- 
tion to determine the distribution of mercury given by inunction, found that it was most abundant 
in the kidneys, liver, and spleen; then in the alimentary canal (least in the stomach and most in 
the large intestine). In the muscles the amounts were variable, in the cerebrum never sufficient to 
be weighed (Internal. Klinisch. Rundschau, 1892, vi.). 

21 



370 GENERAL REMEDIES 

pain is produced; this can be overcome, however, by injecting one- 
quarter of a grain of cocaine immediately before the injection of the 
mercurial into the same spot. The advantages of hypodermic medi- 
cation are the rapidity and power of influence, the cleanliness, and 
the avoidance of gastro-intestinal irritation. 

Mercury is sometimes administered in secondary syphilis in the 
form of fumigations. The patient is placed upon a chair, and sur- 
rounded by a large blanket or, better, india-rubber cloth, so arranged 
as to fit tightly around his neck above, and below to encompass the 
chair. The mercurial preparation is placed upon a metal plate, heated 
by a spirit-lamp, beneath the chair, and the fumes are allowed to fill 
the space around the patient inside of the blanket. The heat produced 
generally causes the patient to sweat profusely, and in from fifteen 
minutes to half an hour the lamp should be withdrawn and the patient 
allowed to cool off, and after a time be put to bed and wrapped up 
in blankets, with the deposit of mercury still adhering to the skin. 
The fumigation may be practised every other night, or at longer 
intervals, and is believed by some to be especially useful in cases of 
secondary skin eruptions. Calomel, black oxide, and cinnabar are 
the preparations generally used; care must be exercised that the 
patient do not breathe the fumes. 

In advanced secondary and tertiary syphilis the mercurial iodides, 
given by the mouth, are often very useful, but the combination of the 
corrosive sublimate and the potassium iodide is in many cases still 
more efficient. Usually not more than one-twelfth of a grain of the 
bichloride should be exhibited, three times a day. 

It appears to be established that certain disagreeable and, per- 
chance, serious effects may be produced by mercurials when freely 
and continuously used in the treatment of syphilis, against which 
the practitioner must be on his guard. The most important of these is 
nephritis, with its consequent albuminuria. According to Heller, the 
safest method of mercurialization, so far as the kidneys are concerned, 
is by the hypodermic employment of corrosive sublimate; the most 
dangerous, probably, being the use of inunctions. A very rare compli- 
cation which has been attributed to the mercury is polyneuritis, which 
has especially been noted after free use of mercurial inunctions.* 

Administration. — For oral administration, when the constitutional 
effect is desired, either of the chlorides or of the iodides may be em- 
ployed. For hypodermic use the corrosive chloride is probably the 
best preparation (see p. 369). 

Mercury with chalk is much used as an intestinal antiseptic in 
inflammatory conditions of the bowel. 

The mercuric oxides are used upon ulcers, chancres, etc., for their 
local effects, and are stimulant and alterative when diluted, mildly 
escharotic when in powder. f From yellow oxide is made the oleate. 

* See Leyden (Deutsch. Med. Wochen., 1893, xix.) and R. von Engel (Prager Med. Wochen., 
1894, xix.). 

t For severe poisoning by yellow oxide, see Brit. Med. Journ., Sept. 1889. 



ALTERATIVES 371 

The oinl ments of the oxides, also the oinl menl of I be nil rate sometimes 
known as Citrine Ointment very generally require dilution with lard, 
and are much used in chronic skin affection*, in obstinate conjunctivitis, 
in psorophthalmia, etc. 

Turpeth Mineral, or Yellow Mereurie Subsulphate, which was 
formerly official a lemon-yellow powder, sparingly soluble in water — 
is a compound of uncertain composition, which was at one time used 
as an emetic in croup. It is, however, a very dangerous remedy, since, 
if it fail to vomit, it may cause a fatal ^astro-enteritis, especially in 
the young child. Two cases of such character are recorded by A. 
McPhedran. Forty grains have caused death in the adult; profuse 
salivation came on in six hours. Dose as an alterative, one-fourth to 
one-half grain (0.016-0.032 Gm.); as an emetic, for a child two years 
old, two grains (0.13 dm.), repeated in fifteen minutes, if necessary. 

Black Wash and Yellow Wash, two non-official but favorite prep- 
arations, are respectively made by the addition of a drachm of calomel 
to a pint of lime-water, and of half a drachm of corrosive sublimate to 
a pint of lime-water. The} 7 depend for their virtues upon the black 
and yellow oxides of mercury, and are used exclusively as local appli- 
cations to chancres and other sypkilitic ulcers. The yellow wash is 
much the more stimulating of the two. 

Solution of Arsenous and Mercuric Iodides contains one per cent, 
each of- the arsenous iodide and the red mercury iodide. It was origi- 
nally suggested by a surgeon of Dublin, by whose name it is very 
generally known. Donovan's Solution is a powerful alterative, used 
chiefly in very obstinate chronic scaly skin diseases, when the local 
action is of a very low grade, and in chronic rheumatism. It is an 
exceedingly active preparation, very capable of acting as a corrosive 
poison, and when administered a little too freely is said sometimes to 
cause salivation. When applied locally, it acts as a violent irritant. 

Toxicology. — The bichloride of mercury (corrosive sublimate) 
and the biniodide (red mercuric iodide) are each so intensely irritant 
in their local action that they may give rise to acute poisoning which 
frequently proves fatal. On account of its wide use as a disinfectant, 
corrosive-sublimate poisoning is by no means rare. The symptoms 
are those of irritation of the alimentary tract and in severity are 
proportionate to the dose. 

If the latter be small, the manifestations may be only some nausea, 
slight burning in the stomach, colicky pains in the abdomen, and 
diarrhoea. After large doses these symptoms are intensified. The 
subject first experiences a peculiar metallic, coppery taste at or shortly 
after swallowing the poison. If the solution be concentrated, degluti- 
tion is interfered with by a spasm of the muscles of the throat and 
larynx, causing a feeling of suffocation, and sometimes even the 
rejection of the draught. Then burning pains are experienced in the 
oesophagus and stomach, followed by violent vomiting, at first mucous, 
then bilious, and finally bloody, and by severe abdominal pain and 
tenderness, with profuse purging, at first serous in character, but 



372 GENERAL REMEDIES 

afterwards affording only small, mucous, bloody stools, which are 
often voided with much straining. The breath generally becomes 
fetid and offensive in a very short time. In the course of two or three 
hours, very rarely in less than an hour, collapse occurs, with small, 
frequent, irregular pulse, pinched, anxious face, cold extremities, 
and finally death, preceded, it may be, by fainting, convulsions, and 
coma. The urine is very much lessened in quantity, is sometimes 
albuminous, or even bloody, and not rarely is suppressed. If the 
patient survive several days, a petechial eruption may appear, and 
salivation sometimes, but not always, occurs. In some cases, after 
the collapse there is an attempt at a febrile reaction, which soon, 
however, gives place to a second and fatal prostration. When recovery 
occurs after severe poisoning, the convalescence is slow and protracted. 

In the treatment of corrosive sublimate poisoning the most avail- 
able antidote is some form of albumin, as white of egg, hashed meat 
or milk. After this opium and tannic acid should be used to quiet 
the vomiting and purging, and stimulants given as required. Demul- 
cent drinks for the soothing of the gastric inflammation, and general 
sustaining treatment will be required during the long and difficult 
convalescence. 

In regard to chronic poisoning with corrosive sublimate, sufficient 
has been said under the general heading, except that colicky pains 
and abdominal disturbance are more apt to occur with it than with 
the less irritating preparations. Hemorrhagic nephritis has been noted 
in a number of cases (H. C. Wood, Jr.). Arnozan asserts that chronic 
catarrh of the excretory ducts of the pancreas is a pronounced lesion 
in chronic poisoning of animals. It should be looked for in man, and 
its presence might be of medico-legal value. 

Severe purging, and even fatal poisoning, may result from a 
single external application of this preparation of mercury,* and in 
animals killed by hypodermic injections of it (see experiments of J. 
Rosenbach), diarrhoea and other indications of gastro-intestinal 
irritation are prominent symptoms, — facts which indicate that the 
bichlor de is eliminated unchanged from the alimentary canal. 

GOLD AND SODIUM CHLORIDE. 

This salt of gold (Auri et Sodii Chloridum), which may be obtained 
in large, golden-yellow, prismatic crystals, is, according to the require- 
ments of the U. S. Pharmacopoeia, a slightly deliquescent powder, 
odorless, but having a saline and metallic taste. It is freely soluble 
in water. 

Physiological Action. — The precise action of the preparations of 
gold upon the animal organism is not understood, but it is probable 

* See case reported by Meeres (.Lancet, Sept. 16, 1871), in which a solution (two grains to one 
fluidrachm) was applied with a camel's-hair brush to the head of a child nine years old, for the cure 
of tinea tonsurans. The symptoms were diarrhoea, profuse salivation, and great prostration, ending 
in death. Washing out the vagina with a solution of corrosive sublimate, has caused severe and 
even fatal poisoning. (See H. C. Wood, Jr.) Marx and Sorge found that in pregnant animals acute 
corrosive-sublimate poisoning causes injury not only to the placenta but also to the foetal kidney. 



ALTERATIVES 373 

thai the soluble preparations are mostly irritant poisons, while the 
insoluble preparations arc cither not poisonous or else act slowly 
upon the general system. It is stated that gold and sodium chloride, 
in overdose, produces pain, inflammation, and even ulceration of the 
stomach and bowels, and otherwise acts as a corrosive poison. It is 
affirmed thai the gold preparations, in moderate doses, cause increased 
fulness and frequency of the pulse, and augment the urine and insensi- 
ble perspiration, without interfering with the appetite or the regular 
anion of the bowels; but that, if the dose be pushed too far, general 
irritation is apt to be produced, and inflammation to seize upon some 
organ, according to the predisposition of the individual, and fever 
is developed. 

Therapeutics. — Although gold and sodium chloride has been 
largely used in the treatment of neurasthenia, hysteria and similar 
nervous conditions, there is no good evidence that it possesses any 
therapeutic value in these conditions. It appears to have been intro- 
duced in medicine from the idea that it formed part of the famous 
Keeley cure for the alcohol habit. According to the sworn statement 
of one of the founders of the Keeley Institute,* the Keeley treatment 
contains no gold in any form. 

The gold and sodium chloride h*as been commended by various 
practitioners in scrofula, advanced syphilis, chronic rheumatism, and 
chronic diseases of the joints. Charles G. Stockton asserts that it has a 
special influence upon the lithemic and fatty degenerations which are 
prone to occur in advanced middle life. The salt is also employed 
with alleged excellent results in the various spinal and cerebral scleroses. 

Administration. — The gold and sodium chloride may be given in 
solution or in pill, in doses of one-twelfth of a grain, increased to one- 
sixth or even one-fourth (0.01-0.016 Gm.) three times a day. It may 
also be administered hypodermically, producing some pain, but usually 
no serious or permanent local irritation. In many cases in which it 
has been used the moral effect of the hypodermic injection has 
probably been greater than the direct influence of the remedy. 

Insoluble Gold Preparations. — The oxide, iodide, and other insoluble 
preparations of gold have been recommended as alteratives in scrofula, skin diseases, 
and secondary syphilis of various forms, in doses of from one-fifteenth to one-tenth 
of a grain, three times a day. 

IODINE. 

Iodine is recognized by the U. S. Pharmacopoeia both in the form 
of metallic iodine and in the form of hydriodic acid and many of its 
salts. It is a soft, friable, opaque substance, occurring in crystalline 
scales with a semi-metallic lustre and of a bluish-black color. Its 
odor resembles that of chlorine; its taste is hot and acrid. It is some- 
what volatile at ordinary temperatures, but when heated to 237.2° F. 
melts and emits the beautiful purple or violet vapor to which it owes 



See report in J. A. M. A., 1907, xlix. p. 18G1. 



374 GENERAL REMEDIES 

its name. It is freely soluble in glycerin, alcohol, and ether, but 
requires five thousand times its weight of water to dissolve it. With 
starch it strikes a deep blue color, and this test is so delicate that it 
will indicate the presence of iodine in four hundred and fifty thousand 
times its weight of water. In testing animal liquids, such as urine, 
for iodine, a small quantity of nitric acid should be added to insure 
its being free in the liquid. 

Absolute hydriodic acid is a gaseous substance, a ten-per-cent. 
solution of which is recognized by the U. S. Pharmacopoeia under 
the name of diluted hydriodic acid. This is a clear, colorless fluid, 
with an acidulous taste. The iodides of sodium, potassium, stron- 
tium, ammonium are all official. They are all white crystalline salts, 
freely soluble in water and having a salty, somewhat bitter taste. 
They are all more or less deliquescent. 

Iodine and the iodides form insoluble compounds with most of 
the alkaloids, with the salts of silver, lead and mercury. 

Official Preparations : 

Iodurn Not used internally. 

Tinctura Iodi (7 per cent.) External use only. 

Liquor Iodi Coinpositus [Lugol's Solution] 

(Iodine 5 per cent.; potassium iodide 

10 per cent.) 5 to 10 minims (0.3-0.6 Ox.). 

Unguent um Iodi (4 per cent.) External use. 

Acidum Hydriodicum Dilutum (10 per cent.). 15 to 20 minims (1-1.3 C.c). 

Syrupus Acidi Hydriodici (1 per cent.) 1 to 2 fluidrachms (4-8 C.c). 

Ammonii Iodidum 3 to 20 grains (0.2-1.3 Gm.). 

Potassii Iodidum 3 to 20 grains (0.2-1.3 Gm.). 

Sodii Iodidum 3 to 20 grains (0.2-1.3 Gm.). 

Strontii Iodidum 3 to 20 grains (0.2-1.3 Gm.). 

Unguentum Potassii Iodidi (10 per cent.). . . .External use only. 

Physiological Action. — Local Action. — Metallic iodine, when 
applied to any part of the body, acts as a very powerful irritant, or, 
if in highly concentrated form, as a mild caustic. The tincture stains 
the skin yellow, and causes, if applied with sufficient freedom, smart- 
ing, some erythematous inflammation, and finally desquamation. 
Its repeated application blisters and destroys the cuticle. Upon 
mucous membranes its action is more intense than upon the skin. 

The iodides are absorbed rapidly and circulate chiefly as an iodide, 
according to Lasser, escaping unchanged. Metallic iodine appears 
to unite, to a large extent, with the alkalies of the tissue and to be 
eliminated chiefly in the form of an iodide, but also partly in organic 
combination (E. Harnack). The elimination is usuaLy prompt and 
chiefly through the kidneys, although iodine has been recognized in 
practically all the tissues and fluids of the body, even in serous 
exudates (Leuch). 

Anten finds that absorption of potassium iodide is retarded by the presence of 
mucilaginous substances and hastened by potassium nitrate or sodium chloride 
and that the elimination of a single dose is complete in about forty hours, seventy- 
five per cent, escaping through the kidneys. Iodine has also been recognized in 



ALTERATIVES 



375 



the secretions of the skin by Taylor and according to See may exist, in saliva even 
after it has disappeared in the urine. According to these ant hois the elimination 
is sometimes irregular so that the drug may accumulate in the system, but, in a 
patient under our care, taking daily :>(>() grains of potassium iodide, John 
Marshall recovered daily '_'(>.") grains in (he urine. (See also Elders.) According 
tn Kanuncr and Bin/, the iodides are partially decomposed in the tissues 
liberating free iodine. 

Although the toxic 1 action of iodine has been studied to some 
extent,* we know very little concerning the action of therapeutic 
doses. It is frequently stated that the iodides have the effect of 
dilating the blood-vessels, but nearly all the scientific evidence on 
this point indicates that this belief is incorrect. 

S£e and Lapicquc believe that potassium iodide acts upon the heart like digitalis, 
but that it also dilates the vessels. On the other hand, Stockman and Charteris, 
and Prevost and Binet have found that, unless given in enormous doses, potassium 
iodide has no effect upon the circulation and Rose has found evidence of 
vascular spasm. 

Von Zeissl asserted that the injection of the solution of iodine in sodium iodide 
into the jugular vein produces a temporary increase of pressure in the left auricle, 
with elevation of the pressure in the pulmonary arteries and pulmonic oedema, 
the latter phenomenon being due to narrowing of the vessels by a direct influence 
of the iodine upon their walls. He further affirms that the injection of the iodine- 
iodide solution into the distal end of the carotid causes an increase of the general 
blood pressure, but a much greater increase of the intra-cerebral pressure, the 
result of an oedematous exudation. 

Action on Kidneys, and Excretion. — During its passage through 
the kidneys iodine undoubtedly exerts an influence upon those organs, 
as is shown by its producing albuminuria at times. It is indeed 
asserted that it occasionally causes a true tubular nephritis. The 
evidence as to its effect upon the solids of the urine is both 
contradictory and insufficient. 

Hermann von Boeck found that the ingestion of iodine does not increase notably 
the elimination by the kidneys or bowels. On the other hand, M. Bouchard (quoted 
by See) declares on Ins personal experience that iodine does increase the daily 
elimination of urea, especially in diabetic patients. C. Handfield Jones analyzed 
the urine of six patients taking large doses of potassium iodide, and found in three 
cases diminished and in three cases increased output of nitrogen; the other ele- 
ments of the urine also failed to show any distinct action of the drug. Eugene I. 
Duchesne found that potassium iodide and tincture of iodine notably increased the 
elimination of urea, while sodium iodide was followed by a distinct decrease of 
this excretion. All the preparations of iodine used increased the elimination of 
uric acid. Henrijean and Corin find that almost all of the iodides markedly increase 
the elimination of nitrogen as well as of the phosphates and chlorides. On the 
other hand, A. Haig affirms that the iodides have a marked effect in lessening the 
elimination of uric acid and the urates, and as a result of this diminish the arterial 
tension. I. Wallace has found that the iodide lessens the elimination of lime salts 
through the kidneys; but his analyses were not sufficiently repeated to prove that 
this is a constant effect. 



* For a research upon the physiological action of large amounts of potassium iodide injected 
into the blood, see Arbeiten aus dem Pharmak. Laborator. zu Moskau, i. 125. As it does not seem to 
throw light upon the therapeutic use of the drug, it is not here analyzed. 



376 GENERAL REMEDIES 

Therapeutics. — As an alterative, iodine is of especial value in 
chronic scrofula. In those cases in which there is indolent enlargement 
of the lymphatics, which exhibit no tendency, or but little tendency, 
to suppurate, it is of especial value. Except in very acute cases, 
however, it should always be tried, even when the glands do tend 
towards suppuration, especially as it exerts a very beneficial influence 
upon the ulcers left after suppuration. In other forms of scrofulous 
disease, in chronic enlargements of the joints, and bone affections of 
such nature, iodine is often of great service. As scrofulosis is generally, 
if not always, associated with lowered nutrition and with anemia, 
cod-liver oil and iron in some form should usually be administered as 
adjuvants. At the same time that the drug is exhibited internally 
in these cases, its ointment should be freely applied to the enlarged 
and indurated glands. Experience has demonstrated the value of 
iodine in true goitre. All tumors of the thyroid body are not goitre, 
however; cystic degeneration of it is very common, and is in no wise 
benefited by iodine. It is in simple hypertrophy of the gland that 
iodine used internally and applied externally over the tumor is bene- 
ficial. During the acute stage of enlargement the use of leeches is 
often of great benefit, and whenever much tenderness exists should 
precede the exhibition of the drug. In phthisis iodine sometimes 
does good, but only in the most chronic cases; and inhalations of 
its vapors, as have been recommended by Piorry, can be of service 
only by stimulating the bronchial mucous membrane and the surfaces 
of cavities. When softening is progressing and the lung breaking 
down, iodine appears to hasten the process. 

In certain forms of rheumatism the iodides are of value. In the 
early, active stages of inflammatory rheumatism it is useless; but later, 
when the joint symptoms persist in a subacute form, the iodide comes 
very well into play. In subacute or muscular rheumatism the iodide 
is an efficient remedy. Often when the symptoms are very acute an 
iodide may advantageously be combined with the alkalies, and in 
lingering cases, especially where there is reason to suspect a gouty 
taint, with colchicum. In sciatica, in lumbago, and in rheumatic 
neuralgia following exposure to cold or wet, as in all other forms of 
subacute rheumatism, much is to be hoped for from its use. In 
gout the iodides are of less service than in rheumatism, but in the 
chronic form of the disease, and in the irregular, inherited gout which 
so frequently appears as neuralgia or other anomalous affection, 
they add to the efficiency of small continuous doses of colchicum. 
In rheumatic gout, or rheumatoid arthritis, they should be tried, al- 
though little is to be hoped for from their use. There is a good deal of 
clinical testimony as to the value of potassium iodide given continu- 
ously between the paroxysms of asthma. This disorder appears at 
times to bear a close relation to irregular gout or rheumatism, and it 
is probably under these circumstances that the remedy is efficient. 

In tertiary syphilis, including in the term all cases of syphilitic 
bone, visceral, or nervous disease, iodine is really of inestimable value. 



ALTERATIVES 



377 



It must be given freely, ami. when there is no cachexia, may be advan- 
tageously combined with the mercury bichloride. It is scarcely in 
place here to enumerate all the forma which tertiary syphilis may 
assume; hut an iodide is useful wherever the dyscrasia has existed for a 
length of time.* Recently potassium iodide has been largely employed 
in the treatment of actinomycosis, and seems to exercise in this disease 
a specific action. 

Potassium iodide appears to have the power of promoting absorp- 
tion of serous thuds, and certainly is of value in chronic pleuritis 
with effusion, in chronic pericarditis, and even in chronic hydrocephalus. 
In aortic aneurism large doses of potassium iodide with continuous 
rest in the horizontal position are much used, but its value is 
questionable. 

In various chronic metallic poisonings the potassium iodide is of 
great service. With both lead and mercury it forms double salts, 
which are soluble, and there is very good reason for believing that 
the formation of these salts takes place in the economy, and that 
the metal which has been lying in an insoluble condition in the various 
tissues is taken up and excreted. Severe salivation and ulcerative 
stomatitis have sometimes resulted from the use of the potassium salt 
in those who had previously taken large quantities of mercury ;f 
and in Melsen's experiments, dogs to which insoluble preparations 
of mercury had previously been given without the induction of severe 
symptoms afterwards died under the action of the iodide, the mercury 
also having appeared in their urine. The experiments of Mayencon 
and Bergeret (quoted in the article on Mercury) afford striking 
confirmation of these facts, and seem to render the evidence irresisti- 
ble that the iodide does bring about the elimination of mercury. In 
regard to lead, the researches of Parkes, Melherbe, Sieveking,J and 
Marshall have shown that very frequently in cases of chronic lead- 
poisoning the exhibition of potassium iodide causes the appearance of 
lead in the urine. This chemical evidence is abundantly corroborated 
by clinical experience, so that in all cases of chronic metallic-poisoning 
the persistent use of potassium iodide should be tried. 

Local Application. — As a simple counter-irritant, iodine is very 
frequently employed when it is desired to maintain a mild, persistent 
influence, as in chronic rheumatic affections and sometimes in phthisis. 
For this purpose the tincture is generally preferred, and it should be 
applied freely once or twice a day, or every other day, according to 
the susceptibility of the patient's skin. In various affections of the 
skin iodine has been employed with asserted advantage. In erysipelas 
of the skin very beneficial results have been ascribed to its local use, 
but great care is necessary lest it be applied too strong. We have 
seen very serious results from the destruction by it of the skin in this 
affection. If the full strength of the tincture be used, it should be 



* For complete literature on this subject, see Lieblein, B. K. C, 1900, xxviii. 198. 
t See Budd (Brit, and For. Medico-Chir. Rev., xi. 202) for a striking case. 
t See Stillg's Therapeutics, ii. 735, Blanchard & Lea, 1864. 



378 GENERAL REMEDIES 

applied at first very lightly, and not more than once in the twenty- 
four hours. In psoriasis, in acne, and in parasitic skin diseases it has 
been used, but holds only a second rank among remedies. In a 
similar manner it is employed in various chronic diseases of the mucous 
membranes, such as ozena, leucorrhcea, chronic cystitis, chronic dysen- 
tery, and scrofulous ophthalmia, — whenever, in a word, an alterative, 
stimulant action is desired. In cases of retraction of the gums, with 
consequent loosening of the teeth, Stille recommends the application, 
with a camel's-hair brush, after each meal, of an aqueous solution 
(one grain to a fluidounce) of iodine, the mouth being immediately 
afterwards washed. The most important external use of iodine is 
as a resolvent in cases of indolent glandular hypertrophic enlargement, 
and where there are large watery exudations, as in some forms of 
chronic pleurisy and of diseased joints. 

Iodine has been very largely employed by injection into serous 
cysts, as in hydrocele, for the purpose of exciting inflammation and 
causing obliteration of their cavity; but this use of it is purely surgical, 
and the reader is referred to treatises upon such subjects. In chronic 
empyema the injection of iodine after free exit has been given to the 
pus is often of the greatest service. The solution in the beginning 
should be very weak, containing not more than six grains each of 
iodine and of potassium iodide in a pint of water; with this the pleura 
should be daily washed out, the strength of the solution being gradually 
increased. 

Toxicology. — Metallic iodine on account of its local irritant action 
is capable of giving rise to an acute form of poisoning. 

A form of chronic intoxication, known as iodism, may be caused 
by the administration, over periods of time, of full doses of elementary 
iodine or the salts of hydriodic acid. 

Acute Poisoning. — When taken internally, a single moderate dose 
of iodine causes merely some gastric uneasiness and a disagreeable 
metallic taste in the mouth; when larger amounts are ingested, the 
gastric uneasiness may be intensified into violent vomiting, with 
increased salivary flow, abdominal pains, and even purging. In 
sufficient quantity it is a poison, although very few deaths have been 
recorded as caused by it. The symptoms produced by toxic doses 
taken into the stomach are burning pain in the oesophagus and stom- 
ach, vomiting, purging, smallness of the pulse, general deadly pallor, 
lessening or arrest of the urinary secretion, sometimes violent excite- 
ment with convulsions, and collapse. Twenty grains of iodine are 
said to have caused death, and two drachms and a half have been 
recovered from.* The vomit is yellowish brown or, if starchy matters 
have been present in the stomach, bluish. The injection of iodine 
into the cavities of the body for therapeutic use has several times been 
followed by cyanosis, thready pulse, repeated vomiting of matters 
containing iodine, excessive thirst, salivation, difficult urination, 

* For cases, see Woodman and Tidy, also Miinchener Med. Wochenschr., Feb. 1887. 



ALTERATIVES 



379 



swelling of the eyelids, laryngeal pain, various eruptions upon the 
skin, high fever, and albuminuria. Sudden death may take place 
after some days from heart-failure. 

E. Rose records a death following injection of iodine into an ovarian cyst. 
Very soon after it was given there ensued severe thirst, with great dryness of the 
throat and mouth, and then painless vomiting of watery matters containing iodine. 
The whole surface became very pale, the extremities cyanosed, the radial pulse very 
frequent, but so small that it could not be counted, the urine very scanty, dark 
brown, and rich in iodine. After a time reaction occurred. For three days the 
vomiting persisted, the pulse was very frequent, full and hard, and the cheek put 
on the glow of high fever, but the temperature did not rise above 37.18° C. On 
the fourth day exanthematous blotches, not disappearing on pressure, developed on 
the skin and in the mouth, the sputa became bloody, and menstruation occurred 
two and half weeks too soon. The urine remained scanty, and on the eighth day, 
when all other symptoms save swelling of the parotids had disappeared, still con- 
tained iodine, and was albuminous. On the tenth day, in the midst of apparent 
convalescence, the patient died suddenly. In a case reported by W. O. Culpeper 
two drachms of a tincture used externally on a child of eleven years destroyed all 
the skin from above the knees to below the ankles. After twenty-four hours there 
developed headache, backache, some diarrhoea, vomiting, great thirst, constant 
desire to urinate, suppression of urine, priapism, and giddiness; finally there ensued 
dysentery without rise of temperature, hiccough, hemorrhage from the bowels, 
and great giddiness ending in death on the sixth day. 

In the experiments of Jorg and his pupils, doses of iodine of a grain to a grain 
and a half gave rise to colicky pains, increased appetite, watery stools, an increased 
secretion of urine, malaise, and some headache. When the dose was augmented 
to two grains, a diffused sense of heat and sexual excitement were superadded. 
Other observers have noted this abnormal sexual excitement, and some have stated 
that at times it is succeeded by atrophy of the mamma? or of the testicles. Stille 
affirms that the menstrual fiow may become excessive, or that during pregnancy 
abortion may be caused. 

Very large quantities of iodine are asserted to have been taken 
without serious results. Julia de Fontenelle* tells of a man who 
took two and a half drachms of iodine without experiencing any 
remarkable effects, and Magendie relates the case of a child four years 
old who swallowed ten grains without serious consequences. f 

In the experiments of A. Hoyges and Binz, preparations of iodine, 
potassium iodide, and iodoform in fatal doses produced in the lower 
animals wide-spread fatty degenerations. 

Iodism. — Chronic iodic intoxication may manifest itself in several 
ways. The most common symptoms of iodism, as seen in the United 
States in non-goitrous individuals, are dull pain in the region of the 
frontal sinus, coryza, sore throat, ptyalism, and an eruption upon the 
skin, which is usually an acne, but may take almost any shape. In 
its serious forms it becomes pustular or bulla-like, and may be 
accompanied by much dermatitis, ulceration, and even very violent 
constitutional disturbances. 

A remarkable iodic dermatitis tuberosa has been noted by Besnier, Duhring, 
and R. W. Taylor. In rare cases there is an excessive susceptibility to iodine, often 

* Quoted by Stille" (Therapeutics, ii. 731). 

t For an elaborate, careful study of the action of large toxic doses of iodine upon the lower 
animals, see Hoffman und Hchwalbe's Jahresbericht, 1879, 199. 



380 GENERAL REMEDIES 

accompanied by marked irregularity of the iodic symptoms. Thus, we have seen 
six grains of potassium iodide given in daily dose repeatedly provoke in a man violent 
conjunctivitis with oedema around the eye, beginning unilaterally, but involving 
the whole face in a violent erythema with great subdermal exudation. Iodic acci- 
dents are especially likely to be severe when there is kidney disease, as in a case re- 
ported by F. Wolf, in which forty grains of potassium iodide given in two days 
appear to have produced death. It is further possible that iodic accidents may 
depend upon gastric conditions, since Bjelogolowy believes that his researches 
have shown that when the contents of the stomach have a heightened acidity and 
contain the nitrites, iodine is set free in the stomach from the iodides and produces 
abnormal effects. 

Rilliet (Trousseau's report on his memoir), who has had wide opportunities 
and has apparently studied the subject very closely, describes three forms of iodic 
intoxication: first, that in which the symptoms are those of gastric irritation; second, 
that characterized by nervous troubles, neuralgia, ringing in the ears, convulsive 
movements, disturbed intellection, with coryza, ophthalmia, salivation, vomiting, 
diarrhoea, polyuria, and cutaneous eruptions, and in some cases atrophy of the 
mammae in the female and of the testicles in the male; * third, iodic cachexia, caused 
either by iodine or potassium iodide continuously used for many months. It is 
said to be most easily induced in goitrous persons, and is characterized by rapid 
emaciation, commencing mostly in the face, and severe nervous palpitations of 
the heart, with excessive appetite, which sometimes precedes and sometimes fol- 
lows the loss of flesh. So long as the drug continues to be taken, these symptoms 
continue to progress, and after a time hysteria or hypochondriasis, with insomnia, 
manifests itself. The goitre, the mammae, and the testicles waste away together; 
but if the medicine be suspended and health gradually returns, while the abnormal 
growth reappears the sexual glands remain wasted. It is probable that some of 
the symptoms in these cases are due to principles taken into the blood from the 
wasting thyroid body. The second form of iodism of Rilliet, in which the nervous 
symptoms are prominent, has been spoken of by other authorities; and Brodie 
lias especially noted disturbances of vision and paralysis. In some rare cases neu- 
ralgic pains and other disturbances of nerve-functions have occurred, indicating 
that iodine is capable of causing a peripheral neuritis.f 

Iodipin. — This is a yellow, oily fluid, said to be an iodine addition-product of 
sesame oil, containing ten per cent, of iodine in chemical combination. According 
to H. Winternitz, iodipin when taken internally passes unchanged into the intes- 
tines, where it is slowly digested with an absorption of iodine, probably as an alka- 
line iodide; and the final escape from the intestines of a portion of the iodipin 
unchanged. When it is injected hypodermically it forms a local depot, as it were, 
from which the iodine is very slowly, but continuously, absorbed. Under these 
circumstances it is said to produce no local disagreeable symptoms. Winternitz 
affirms that no absorption of iodine takes place after iodipin inunction or enemata. 
In chronic syphilis it has been used internally in doses of from fifteen to thirty grains 
(1-2 Gm.) of the ten-per-cent. iodipin, which may be injected daily, as recommended 
by Schuster. Naegeli recommends for the purpose of producing local absorption 
subconjunctival injections of one-third to one-half minim (0.02-0.3 C.c.) of iodipin 
in specific retinitis, scleritis, keratitis dendritica, and keratitis neuropamlytica. Dose 
of iodipin, one to two drachms, given in emulsion, three or four times a day. 

IODOFORM 

Iodoform, which was discovered by Serullas in 1822, and intro- 
duced into medicine by Glover in 1837, is a triiodomethane (CHI 3 ), 
being therefore chemically related to chloroform and bromoform. 

* For a case of wasting of the testicles, see Phila. Med. Times, iv. 661. 
t See Therapeut. Monalsheite, 1888, iii. 



ALTERATH ES 



38] 



It occurs as a greenish-yellow powder of crystals, with a powerful 
and persistent odor, practically insoluble in water, sparingly soluble 
in alcohol but freely soluble in ether und in oils. 

Official Preparations : 

[odoformum 3 to 5 grains (0.2-0.3 Clm.). 

Unguent urn Iodoform! (10 per cent.) External use only. 

Local Action. In itself iodoform is a non-irritant, slightly desiccant 
powder, which appears to be imbued with local anesthetic properties, 
so that the rectum may be so benumbed by a suppository containing 
iodoform that defecation may take place without the knowledge of 
the individual. Although it does not, itself, possess any germicidal 
properties, by decomposition and formation of new compounds, 
iodoform becomes a locally active substance. (See page 383). 

Absorption and Elimination. — Iodoform, or the products of its 
decomposition, is absorbed very slowly from the alimentary canal, 
but is taken up from wounds with comparative freedom. It is largely 
destroyed in the system and escapes in a large part as an iodide and 
an iodate, but also partially as a new organic compound of iodine. 
Zeller believes that there is always an albuminous compound of 
iodine formed at the seat of absorption. According to the researches 
of Rummo, the elimination of iodine commences within one hour 
after the stomachic ingestion of the iodoform, and goes on so slowly 
that the haloid can be found in the urine three days later.* 

Physiological Action. — Notwithstanding numerous experiments 
upon the lower animals, further research is necessary before any 
positive knowledge can be reached as to the physiological action 
of iodoform, although it is probable that it acts very much as 
does iodine. 

The symptoms produced by iodoform in the frog are said to be muscular relax- 
ation with sometimes, at a later stage, convulsive movements. In the higher 
animals large but non-toxic doses produce symptoms of intoxication, tottering, weak- 
ness, and loss of appetite, but no vomiting; fatal doses cause anesthesia, narcosis, 
convulsions, with violent opisthotonos, hurried or irregular breathing, slow, feeble 
pulse, and finally death. A. Hoyges found that in dogs and cats toxic doses caused 
deep sleep without loss of reflex activity, but that in rabbits no sleep resulted. 
Very frequently after these large doses, especially when they are repeated, there 
is great gastro-intestinal disturbance, as is shown by vomiting, diarrhoea, and 
dysentery, with bloody discharges. The action of the drug upon the circulation 
has been especially studied by Rummo. He finds that in the frog the rate of the 
cardiac pulsations is lessened, and for a time the energy of the ventricular systole 
is increased, but afterwards the pulsations become feeble, and finally the heart 
is arrested in diastole; the contractions cannot be re-established by the use of atro- 
pine. In the mammal the rate of the pulse is decreased, and after small doses the 
arterial pressure is at first increased. By large doses the pressure is much diminished. 
Section of the pneumogastrics does not affect the cardiac action of the drug. After 
very large doses there are albuminuria and even hematuria. 



* For an important bibliography, see the paper of M. Rummo. For details as to elimination 
and discussion of methods of finding the iodine in the urine, consult Harnack (Zeita. f. Pyniol. 
Chem., 1884, viii. 158), A. Zeller and E. Baumann (Verkandl. Deutach. C'csetl. f. Chemie, Berlin, 
1882, xi. 219). 



382 GENERAL REMEDIES 

These various researches would indicate that the iodic compounds 
liberated by iodoform are universal poisons, and that the conclusion 
of Rummo is correct, — namely, that iodoform acts upon almost all 
the tissues, but primarily upon the nerve-centres and subsequently 
upon the nerve-trunks and on the muscles. 

Therapeutics. — At one time iodoform was used to a considerable 
extent as an internal alterative and analgesic in chronic syphilis, 
especially when there were severe rheumatic, neuralgic, or night-pains. 
It has also been employed as an absorbefacient substitute for iodine 
in various lymphatic tumors and serous effusions. It seems to have, 
however, no superiority over the simpler iodine preparations, and to 
be much less certain and definite in its action, so that its internal 
use has passed completely out of vogue. 

On the other hand, as a local remedy, it has continuously asserted 
itself in the face of very numerous substitutes, and is still largely 
used. It is useful in cases of painful ulcers, even when they are 
cancerous, serving to alleviate pain and to promote cicatrization. 
At first employed especially in syphilitic affections, it is now known 
to act equally well in indolent leg ulcers, in burns* and in other non- 
specific abrasions, and it is thought to be not only a local anesthetic, 
but also a decided stimulant to nutrition. Within the last few years 
it has been very freely employed as an antiseptic dressing to wounds, 
and the testimony is so strong that it is difficult to avoid believing 
that it is one of the most reliable of the antiseptics. It is employed 
either in the form of powder dusted in the wound, or as dressings 
saturated with it, the first method being at once the more effective 
and the more dangerous. 

As a local anesthetic it is especially useful in rectal diseases, as 
hemorrhoids and anal fissures. It may be applied as an ointment or 
in the form of a suppository. 

The danger of iodoform-poisoning in a surgical case varies not only 
with the amount of iodoform used, but also with the form of the 
iodoform and the seat of the application. The more finely powdered 
the iodoform the greater its activity, and serious absorption is 
especially likely to take place from the peritoneal surfaces. f 

In 1886 Fiirst described furuncular and eczematous inflammation 
produced by the contact of iodoform with the skin. Krevet affirms 
that this irritation can rapidly be relieved by momentary applications 
of very hot water to the part. 

The good results which have followed the surgical use of iodoform 
as an antiseptic dressing have led to a series of investigations as to 

* Burns, Treatment of. — At a discussion of the International Congress of Dermatology, in 
1889, the conclusion was reached that the best treatment of burns in the beginning is to cut the 
bullae, wash the part with a very weak solution of salt, and then dress with iodoform gauze, or a 
pomade of iodoform, and cover with oil-silk. In the later stages, after the separation of the eschars, 
according to Hebra, iodoform retards cicatrization while a one- or two-per-cent. solution of resorcin 
hastens epithelium formation. 

t In a case in which an extensive intra-peritoneal dressing of iodoform gauze was used, and 
seven grains of calomel given by the mouth, violent irritant poisoning, with numerous bloody 
mucous stools at short intervals, occurred, evidently as the result of the formation of the mercurous 
iodide in the alimentary canal. — F. F. Simpson in a letter. 



ALTKKAT1YKS 



383 



its action on the lower organisms, with results which are apparently 
at variance with previous surgical teachings. In November, 18S6, 
De Ruyter announced at a meeting of the Berlin Surgical Society 
that the powder of iodoform has little or no effect in preventing the 
development of bacteria, and that when it is mixed with rapidly 
infective bacteria, like those of anthrax, it does not sensibly influence 
the development of the disease which is caused by inoculation with 
the mixture. 

This has been confirmed experimentally by Kronaehcr, who employed the 
bacteria of erysipelas and of anthrax; also by P. Baumgarten,* who further found 
that iodoform powder mixed with the tubercle bacillus in cultivating apparatus 
did not prevent its ordinary development, and that the bacillus mixed with iodo- 
form powder when introduced into guinea-pigs and rabbits produced rapid tuber- 
culosis; also by Liibbert, with the Staphylococcus pyogenes; also by Heyn and 
Thorkil Drovsing, who found that iodoform has no influence upon the development 
of the Staphylococcus pyogenes or of the coccus of pneumonia or of the Bacillus 
subtilis and other organisms, and conclude that it is not only worthless as an anti- 
septic, but may even be the moans of carrying the septic-organisms into the system; 
also by Johann Olsen, with various bacterial organisms; also by Konige. On the 
other hand, II. Sat tier, in his experiments, found that when he impregnated threads 
with iodoform and micro-organisms and then placed them in culture-apparatus, 
the iodoform had a very distinct effect in checking the development of the bacteria, 
and De Ruyter states that if instead of using the iodoform powder he employed an 
ethereal solution in which decomposition of the iodoform had already commenced, 
there was a distinct effect upon the organisms. In a further series of experiments 
De Ruyter showed that iodoform is decomposed by blood, serum, and other organic 
fluids in winch micro-organisms are growing, and apparently proved that the de- 
composition is produced by the ptomaines developed by the growing organisms. 
These general results have been abundantly confirmed; f the antiseptic properties 
of iodoform depend upon its decomposition, and its action is most favorable when 
the processes of fermentation and of chemical activity are most energetic. t 

The clinical results achieved by surgeons are so concordant and 
so decided that the practical value of iodoform in the treatment of 
wounds and ulcers must be considered established. It is possible that 
a part of the good influence of the iodoform is due to a specific effect 
upon the tissues of the wounds. Further, the powder of iodoform 
may have a very distinct protecting power both mechanically and 
by the dryness of the wound which it maintains, the discharges from 
the wound being the especial soil in which the bacteria develop. In 
tubercular diseases iodoform appears to exert a direct influence upon 
the bacilli. Many clinicians bear strong testimony to the effect of 
iodoform on tubercular ulcers of the larynx and other organs. Accord- 
ing to Bruns, the first change which results from the use of iodoform 
in a tubercular abscess is the disappearance of the bacilli and appear- 

* A curious fact made out by Baumgarten was that rubbing the bacillus of anthrax with any 
hard powder apparently mechanically kills the organism. 

t See especially Neisser (Virchow's Archiv, ex.), Schnirer (Wien. Med. Presse, 1887, ex.), and 
Kuntz (Beitrage Path. Anat. u. Physiolog., 1888, ii.). According to the experiments of Altenberg 
(A. I. P. T., 1901, viii.), the blood, serum, and urine do not liberate free iodine from iodoform, 
although the tissues of various organs, even when dried and powdered, have the property of so 
doing. It seems to us probable that these tissues depend for their activity upon the presence of 
micro-organisms. 

t Moeller has found that the iodates and iodic acid cause symptoms similar to those produced 
by iodine (Inaug. Diss.. Bonn, 1877), and Schwerin has shown that methyl iodide is also anesthetic 
and hypnotic (Centralbl. f. Med. Wissensch., 1884, 146). 



384 GENERAL REMEDIES 

ance of the normal granular tissues. The value of iodoform as a 
local application in surgical tuberculosis seems to be firmly established. 
In the treatment of tuberculous abscesses, in tuberculous empyema, 
in tuberculous joints, in non-suppurating tuberculous glands, and even 
in tuberculous peritonitis numerous cures have been reported. That 
the iodoform has a specific influence upon the tubercular organism 
would seem to follow from the experiments of Gosselin, of Caen, who 
found that guinea-pigs saturated with iodoform are incapable of 
contracting tuberculosis. The manner of application varies with 
different surgeons. Verneuil, who has had an enormous experience, 
prefers, in the treatment of abscesses, tuberculous glands, and in most 
other cases, the injection of a five-per-cent. ethereal solution. Others 
prefer glycerin as a menstruum, especially in empyema; while others, 
particularly in peritonitis, dust the dry powder over the portion which 
has been laid open. 

Administration. — Iodoform may be applied to ulcers in powder, 
in solution, or in ointment. When there is a great deal of pain, espe- 
cially if there be much discharge, the powder is to be preferred; not 
more than half a drachm of iodoform should ordinarily be applied 
to a wound, although in cases of tuberculosis the surgeon is more than 
warranted in taking the risk of larger amounts. Verneuil injects at 
one sitting never more than seventy-five grains of the iodoform. 
There is certainly much truth in the criticism of Kobert, that proba- 
bly in most cases one-tenth part of the amount of iodoform habitually 
employed by the surgeon would suffice for all therapeutic purposes, 
and that many lives are unnecessarily endangered by the excessive 
amount of the drug used. In uterine cancer and in painful hemorrhoids 
cacao-butter suppositories, containing from five to ten grains of the 
drug, may be employed. They are also often very valuable in reliev- 
ing dysenteric and various irritable neurotic conditions of the rectum. 
Owing to the bad odor of the drug, its application about the mouth 
and throat is often objected to. 

According to Lewis Elsberg, if to four parts of absolute ether one part of crys- 
tallized iodoform be added, and the whole shaken in a red glass flask, a solution is 
obtained of sufficient strength for effectual use in diseases of the mouth, and free 
frori odor other than that of ether. Olive oil, saturated with camphor, is said to 
dissolve rix per cent, of iodoform, and is preferred by some surgeons. 

Toxicology. — In the largest therapeutic doses (five to six grains) 
iodoform produces no symptoms, and we know of no cases of poison- 
ing by its internal administration. On the other hand, its surgical 
use has led to a number of fatal poisonings. The symptoms, as 
recorded, have been very various. They may be preceded by general 
malaise for a day, and then suddenly burst forth.* In the most 
characteristic and severe class of cases the phenomena resemble 
somewhat those of meningitis, and may be somnolence, deepening 

* Case, Deutsch. Med. Wocliensclir., ix., 443. 



ALTERATIVES 386 

Into stupor, with contracted, motionless pupils, or restlessness, ending 
in active delirium, in either case the temperature being normal and 
the pulse exceedingly rapid. A peculiarity of these cases seems to 
be that death usually follows, although the symptoms have developed 
abruptly and the dressings have been removed at once. Schede, 
of Hamburg, describes six classes of cases, his sixth form being that 
just spoken of. 1. High fever, without other phenomena. 2. Fever, 
with mild gastro-intestinal irritation, depression of spirits, and 
rapid pulse; recovery almost invariable. 3. Very rapid, soft pulse, 
150 to ISO, no fever; great danger. 4. Very rapid pulse, with high 
fever; death almost invariable. 5. After severe operations, rapid 
collapse and death. A form of poisoning with melancholia, dilated 
pupils, and hallucinations is also described. A roseola-like dark red 
eruption has been noted in some cases of poisoning (Anschutz has 
seen violent acne); even when the constitutional symptoms are very 
slight there may be an extensive erythema.* Convalescence may be 
very protracted, the patient remaining in a condition of uncon- 
sciousness or semi-consciousness for some days, with complete loss 
of memory and some evidences of mental disturbance. Accord- 
ing to De Schwcinitz, iodoform has rarely produced amaurosis or 
amblyopia with scotomata. 

On account of the indefhuteness of the symptoms of iodoform- 
poisoning great importance attaches to any positive means of recog- 
nizing the nature of the illness. Burlureaux affirms that if a piece 
of silver be placed in the mouth of a person suffering from iodoform- 
intoxication, the taste of garlic will be immediately perceived, and 
that if some of the saliva be mixed with calomel, a canary-yellow 
precipitate of mercurous iodide will be obtained; according to Sasse, 
if a pinch of powdered calomel be placed upon a saucer, and a few 
drops of the urine from a case of iodoform-poisoning be mixed with 
it by means of a glass rod, the yellow color will appear (yellow iodide). 
These tests prove only that the patient is under the influence of some 
compound of iodine, but, if correct, must in many cases be sufficient 
for the purposes of the practitioner. 

After death from iodoform a very wide-spread fatty degenera- 
tion is to be found. This change appears to commence in the liver 
and rapidly to involve all tissues of the body. Floucaud states that 
there is a very distinct alteration of the blood-corpuscles. 

The quantity required to take life is uncertain. Langenstein 
attributes a death to four grammes; the cause of the death seems, 
however, doubtful. Czerny reports death from six grammes. 

Treatment. — Whenever any suspicious symptoms arise during 
the use of iodoform, the dressing should immediately be removed 
and the part well washed with warm water. The assertion by Sampter 
and Retzlaff that the potassium bromide is a chemical antidote by 
virtue of its dissolving iodine compounds, has, so far as we know, 

* Cases, Intern. Cong., Copenhagen, 1884, Sect. Dermatol., 118. 
25 



386 GENERAL REMEDIES 

received no clinical or experimental confirmation, and there appears 
to be no other treatment of iodoform-poisoning than the free internal 
use of water, with the hope of aiding in the elimination of iodine 
compounds and the meeting of symptoms as they arise. 

IODOL. 

Tetra-iodopyrrol or iodol, which is made by the action of iodine 
upon pyrrol, is a yellowish-brown, shining powder, composed of long, 
prismatic crystals, soluble in three parts of soluble alcohol, in ether, 
and in fatty oils, but soluble in water only in the proportion of 1 to 
5000. It is tasteless and without odor. It contains 88.9 per cent, 
of iodine, as contrasted with 96.7 parts contained in iodoform. First 
discovered by Silber and Ciammican, it was proposed as an antiseptic 
by G. Mazzoni, of Rome. It causes in the lower animals (Marcus 
and T. Pahl) emaciation, albuminous urine, fall of temperature, 
general loss of muscular power, and finally death from fatty degen- 
eration of the liver, kidneys, and other tissues. The assertion that 
it is not capable of producing constitutional symptoms is not correct. 
C. Langenstein reports, as caused by the surgical use of the drug, 
dizziness, marked rise in the temperature, vomiting, small irregular 
pulse of 136 per minute, albuminous urine, and apathy, which did not 
subside for four days. Iodine was found in the urine for two weeks. 

In the experiments of Seifert, iodine was first detected in the urine and saliva 
twelve hours after the ingestion of seven and a half grains, did not reach its maxi- 
mum until eighteen hours, and continued present for three full days; this accords 
with the statement of Pick that iodol is absorbed very slowly. This slow absorp- 
tion is probably the reason that it is a less dangerous topical application than is 
iodoform. 

Cervesato affirms, with . doubtful correctness, that in man iodol, 
taken internally, acts like iodine preparations, but never causes iodism. 

Therapeutic Use. — Iodol may be emploj^ed for all purposes 
for which iodoform has been used. Mazzoni 's solution was: iodol one 
part, alcohol sixteen parts, glycerin thirty-four parts. One drachm 
of iodol forms with one ounce of ether a clear brown solution, which 
may be applied by the spray or brush to the nasal and other mucous 
membranes, upon which it leaves a coating of iodol. Iodol has also 
been used as an internal remedy. According to Assaky, iodol is very 
effective in tertiary syphilis in doses of from six to thirty grains (0.4r-2 
Gm.) a day. 

THYMOL IODIDE. 

Dithymol-Diiodide frequently called by the trade name of Aristol, 
containing 45 per cent, of iodine, is a light, reddish-brown, crystalline 
powder, with a slight aromatic odor, insoluble in water, very soluble 
in fats and ether, slightly soluble in alcohol. According to Neisser, 
Quinquaud and Fournioux, and Eichhoff, when introduced even in 
very large amounts into mammals it produces no serious intoxica- 



ALTERATIVES 387 

tion. The method of its elimination lias not been made out. Quin- 
quaud and Fournioux succeeded in demonstrating the presence of 
iodine in the urine of animals to which it lias been freely given, but 

wore not able to discover traces of thymol. The experiments of 
Neisserseem to show that it has no influence upon the lower organisms. 
ami it cannot be considered, therefore, as directly antiseptic. It has 
been employed by a number of practitioners with asserted good results 
as a local application in inflammations of the mucous membranes of 
the nose and upper air-passages, especially when there is absence of 
secretion; also in psoriasis, in lupus, in various syphilitic lesions, and 
as a substitute for iodoform in the treatment of ivounds. It appears 
to be free from irritant properties, and may be used in a strength 
varying from ten per cent, to the pure powder. 

Through the ingenuity of pharmaceutical chemists there have been put upon 
the market a number of iodine compounds, very few of which have real value. 

Nosophen, the acid tetra-iodo-yhenol-phthalein, is an impalpable, yellow-gray, 

odorless, tasteless, insoluble powder, containing sixty-one and seven-tenths per cent. 
of iodine. Its sodium salt, Aiitinosine, is a dark blue amphorus powder, readily 
soluble in water and alcohol. Its bismuth salt, Etuloxinc, is a reddish-yellow, taste- 
less, odorless, insoluble powder. It is alleged that nosophen and antinosine arc not 
decomposed in the human body, while eudoxine is slowly changed by the alkaline 
juices of the intestines into antinosine and bismuth. It is alleged also that they are 
germicides. As intestinal antiseptics, eudoxine being the best, they may be given 
in doses of five to eight grains (0.3-0.5 Gm.). 

Locally, antinosine, on account of its solubility, is preferred as an application 
in infective inflammations of the mucous membrane, the strength of its solution 
varying from one to three per cent. According to Binz and Zantz, when given 
intravenously, antinosine is decomposed and nosophen precipitated in the blood. 

Europhen, di-isobutyl-ortho-cresol-iodide, is a yellowish amorphous powder, 
containing twenty-eight and one-tenth per cent, of iodine, which is stated to be 
decomposed more slowly than iodoform, and to be therefore less poisonous. Taken 
internally, it escapes unchanged in great part or altogether with the feces, and is 
said to be non-toxic, fifteen grains producing no effect in human beings. Exter- 
nally, it lias been employed to a considerable extent as a substitute for iodoform, 
but appears to have some irritant properties. 

Soziodol, di-iodoparaphe?iolsulphonic acid, contains thirty-one and a half per 
cent, of mercury and thirty-eight per cent, of iodine; it has been used as a local 
irritant, chiefly employed in the form of a powder (talc), fifteen per cent. The 
assertion of A. Lubbert, that it is as active as corrosive sublimate as a germicide, 
and free from poisonous properties, has not been confirmed. 

Iodoformogen, a compound of albumin and iodoform, nearly free from odor, 
is a light yellow powder, insoluble in water, which has been used as a substitute 
for iodoform. 

COD=LIVER OIL. 

Cod-liver oil is obtained from the liver of Gadus morrhua and 
of other species of Gadus. In the manufacture of the so-called Shore 
oil, the only variety employed in medicine, the fish caught near land 
are brought at once to the shore, and the oil is obtained by forcing 
-team at high pressure through a mass of the fresh livers enclosed in 



388 GENERAL REMEDIES 

a metallic vessel, so as to tear them into pieces and melt out the oil. 
Cod-liver oil for medicinal purposes should always be perfectly limpid, 
yellow, free from rancidity, and have the peculiar taste and smell of 
the oil well developed. The cruder varieties, sometimes known as 
Straits or Banks oil, used in the preparation of leather and for other 
purposes in the arts, are prepared by allowing the livers to stand in 
casks and undergo putrefaction until the oil rises to the top, when it 
is skimmed off. The black or brown oil which results is extremely 
disgusting both in odor and taste, and is loaded with the products 
of decomposition. 

Cod-liver oil is a very complex substance, containing glycerin, 
oleic, margaric, butyric, and acetic acids, gaduin, various biliary 
principles, iodine, chlorine,- traces of bromine, phosphorus, phos- 
phoric acid, and a peculiar ammoniacal base, trimethylamine (com- 
mercial propylamine), which exists in no other official oil, but occurs 
in ergot. According to the U. S. Dispensatory, the proportion of 
iodine never exceeds 1 part in 2000. Gaduin is a peculiar, dark brown 
substance, which is probably medicinally inert. 

Official Preparations: 

Oleum Morrhuae 1 to 4 fluidrachms (4-15 C.c). 

Emulsura Olei Morrhuse (50 per cent.) 1 to 8 fluidrachms (4-30 C.c). 

Emulsum Olei Morrhuse cum Hypophosphi- 

tibus (50 per cent.) 1 to 8 fluidrachms (4-30 C.c). 

Physiological Action. — As is well known, all fatty substances 
when taken into the system have a tendency to cause deposition or 
formation of fat in the body. Cod-liver oil certainly shares this 
property in an eminent degree. Pollock (quoted by Stille) has found 
that if there be given of it to pigs from one to two ounces per diem, 
to sheep one ounce, and to bullocks from three to nine ounces, it is 
digested, and aids in fattening the animal; larger amounts than those 
noted in Pollock's experiments always derange very seriously the 
digestive function. No close studies of the effect of the cod-liver 
oil upon healthy men have been made. Undoubtedly it tends to 
produce obesity; but, as no other oil is able to supply its place in 
various chronic diseases, it must have some influence upon nutrition 
not shared by ordinary fatty matters, and therefore is an alterative. 

The history of the clinical use of cod liver oil certainly indicates 
that it influences the constitution of the blood. It is an every-day 
occurrence to see pale, anemic patients become, while taking it, rosy 
and plethoric. According to the analysis of the blood of a patient 
made by Simon, there is, during its use in phthisis, a great increase 
in the amount of solids in the blood, a diminution of the fibrin, and 
an increase in the albumin. The examinations of Dugald Campbell 
have confirmed the results of Simon. It is very probable that cod- 
liver oil has some peculiar influence upon the blood-making organs. 
Upon the various single functions of the body, except the digestive, 
cod-liver oil has no apparent immediate effect, disturbing directly 



\LTERATIVES :\su 

neither the aervous, motor, respiratory, circulatory, nor secretory 
movements. When by its use the general nutrition is improved, 
nil the functions seem to share equally in the improvement. Cod- 
liver oil has undoubtedly, when given with sufficient freedom, a 
tendency to cause indigestion and looseness of the bowels. All oils 
are of difficult digest ion. and when too much of the oleum morrhus 
1S exhibited in man, as in animals, it exerts a deleterious local effect 
upon the alimentary apparatus. 

Much speculation has been indulged in as to which of the ingre- 
dients of cod-liver oil impart to its peculiar medicinal properties.* 
Certainly, however, no conclusion has been established, and the pres- 
ent probabilities are that it acts as a whole, — i.e., that its virtues 
depend upon the peculiar combination. 

The experiments of Oswald Niuunann indicate that the physical properties of 
cod-liver oil aid in its usefulness. He first tested the rate at which various oils pass 
through fresh moist animal membranes when pressed upon by a column of mercury 
or by the weight of the atmosphere over an exhausted receiver, and found thai 
cod-liver oil passed much more rapidly than did any of a number of oils tried. Ap- 
parently this power depended in some measure upon the presence of the biliary 
principles, since if it was deprived of them the rale of its passage was greatly lessened, 
but was again increased by the addition of a little bile. The investigator then, 
opening the abdomen of cats, separated in each animal by ligatures two knuckles, of 
equal length and entirely similar, from the remainder of the intestines. Into each 
of them he injected a certain amount of bile, and then into one ordinary oil, into 
the other cod-liver oil; and when the animals died, some hours afterwards, it was 
always found that much more of the cod-liver oil was absorbed than of the other oil. 
Kallmann's experiments were too few and incomplete to be decisive, but they accord 
with the clinical observation of Berths, who found that cod-liver oil could be taken 
longer than other fats without appearing in the feces; observations wliich have been 
confirmed by Bucheira, as well as by J. Gad. Both Bucheim and Gad believe that 
this absorbability depends largely upon the presence of free fatty acids in the oil, 
but it is probably due to the biliary matte; \ since H. A. Hare finds it greatly in- 
creased by the addition of taurocholate ana glycocholate of sodium. Hare asserts 
that cod-liver oil impregnated w r ith a small quantity of the biliary salts is rapidly 
absorbed when rubbed upon the skin, and proposes the practical use of the mixture. 

Xaumann's last series of experiments were directed to discovering the com- 
parative, ease with which animal oils and the cod-liver oil were oxidized. For this 
purpose he used a test -solution of potassium permanganate, and on adding to given 
bulks of this, in test-tubes, equal amounts of the various oils, noted the changes of 
color induced by the reduction of the permanganate. He found that cod-liver oil 
was the first to be affected. 

It is evident that the power of being easily absorbed and easily 
oxidized fits a fat for use in the animal economy; but even if cod- 
liver oil possesses these properties to a remarkable degree, it is clear 
that they cannot be the chief causes of its peculiar influence on disease. 

Therapeutics. — Cod-liver oil is a valuable remedy in various 
conditions of emaciation not dependent upon diseases of the ali- 

* A Gautier and J. Bouillot assert that they have found in cod-liver oil certain alkaloids which 
are stimulants to the circulation and to the nutrition, and also to the kidneys, and to which are 
largely or altogether due the peculiar properties of the oil. These alkaloids have been used in 
practical medicine by J. Bouillot, who affirms that 0.15 to 0.25 gramme given during the twenty- 
four hours powerfully stimulates nutrition, increasing very much the amount of the urine and 
also the nitrogenous elimination, especially of the completely oxidized nitrogen. 



390 GENERAL REMEDIES 

mentary canal or upon cancerous affections. It has been extensively 
used in various forms of scrofula and tuberculosis and where it does 
not disturb digestion is useful as a food of high caloric value. It has, 
however, no specific relations with the tubercle bacillus, acting only 
by stimulating the nutrition of the human organism. It is similarly 
effective in various non-tubercular conditions of defective nutrition 
as it is in phthisis. It is especially valuable in rickets. It is often of 
service in advanced tertiary syphilis with wasting cachexia. It first 
achieved its reputation as a remedy in chronic rheumatism. In neu- 
ralgia and in various skin diseases it may at times be used with great 
advantage. It is not the disease, but the general condition of the 
nutrition which should influence the practitioner in the employment 
of this remedy. 

Administration.— The chief difficulty in the use of cod-liver 
oil is the very common, real or imagined, inability of the patient to 
take it. Without doubt, this very often arises from its nauseous 
taste, to lessen or disguise which various expedients are resorted to. 

Sometimes a piece of salt taken into the mouth just before the oil, which is 
also immediately followed by another lump of salt, suffices. It is said that some 
prefer the oil in emulsion made with some strong aromatic water. The addition of 
an equal part of glycerin and one-half to one drop of the oil of bitter almonds to the 
dose certainly lessens the taste of the medicine. In cases where alcohol is also 
indicated a successful plan of exhibition is to place, according to the exigencies of 
the case, from one to three tablespoonfuls of whisky or brandy in a tumbler, add 
a small amount of water, put the oil in the centre, and toss the whole down the throat, 
the head being held well back, the mouth wide open, and the lips not touched by 
the medicine. The stimulus of the alcohol often enables the stomach to digest the 
oil when otherwise it could not do so. Sometimes it is necessary to commence with 
a single small daily dose, even a single teaspoonful, which is best taken at bedtime, 
and gradually to increase the amount as the patient becomes habituated to it. 
Children almost always learn to tolerate the taste of the oil, or even become in a 
short time fond of it. 

When infants cannot digest cod-liver oil, inunctions may some- 
times be practised with advantage. N. A. Randolph and A. E. Roussel 
state that they have seen, in such cases, the oil appear in the feces. 

COLCHICUM. 

Colchicum autumnale or meadow saffron, is a small plant belong- 
ing to the lily family, found in Europe and England. The official 
portions are the seeds and the corm. The latter which is often in- 
correctly called the root, is the thickened, swollen end of the stem 
with the little tuber attached, whose office it to develop a new plant. 
This corm is solid and fleshy, an inch and a half to two and a half 
inches in length, with a longitudinal groove, having a nail-like process 
(the bulblet) at its base. In the shops it is very commonly kept in 
transverse slices, which are notched and cordate; the taste is bitter, 
hot, and acrid. Colchium seeds are nearly round, about an eighth 
of an inch in diameter, and of a bitter, acrid taste. Colchicum depends 



ALTERATIVES 391 

for its activity upon the presence of an alkaloid colchicine,* of which 
the seeds should contain 0.45 per cent, and the corm, 0.35 per cent. 
Colchicine exists in the form of pale yellowish globules, or as an amor- 
phous powder. It is soluble in 22 parts of water, freely soluble in 
alcohol and chloroform. 

Official Preparations : 

Kluidext lactam Colchici Seminis 2 to 6 minims (0.1-0.4 C.c). 

Tinctura Colchici Seminia (10 per cent.). J to 1 fluidnichm (2-4 C.c). 
Vinuin Colchici Scminis (10 per cent^.). . . \ to 1 fiiudrachm (2^1 C.c). 

Extractum Colchici Conni i to 2 grains (0.03-0.10 Gm.). 

Colchicine T J 7 to -fe grain (0.6-1.3 Milligm.). 

Local . 1 ction. — Absorption. — Elimination. — Although preparations 
of colchicum brought in immediate contact with the mucous mem- 
brane do not seem to be immediately and actively irritant, yet when 
taken internally they produce violent gastro-intestinal irritation 
which is probably closely connected with attempts at elimination. 
Concerning the elimination of the active principle of the drug we 
have little knowledge, although it can scarcely be gainsaid that the 
alkaloid escapes with the urine and, when in toxic dose, probably 
more largely with the gastro-intestinal secretions. 

Physiological Action. — No distinct symptoms are produced by 
the smallest therapeutic doses of colchicum. After somewhat larger 
amounts there is gastro-intestinal disturbance, as shown by abdom- 
inal uneasiness, colicky pains, borborygmi, loss of appetite, moderate 
purging, and sometimes nausea, — symptoms differing in degree only 
from those of poisoning by the drug. Before these come on, however, 
there is a lowering of the pulse-rate, sometimes as much as twelve 
beats per minute, which, according to some authorities, is sometimes 
accompanied by free diaphoresis, though it has never been our experi- 
ence to see this symptom. Any nervous symptoms, such as vertigo, 
headache, or muscular weakness, which may be present as the result 
of the administration of colchicum are probably sympathetic from 
the gastro-intestinal irritation. 

The physiological effect of a single full dose of colchicum is not 
yet clearly demonstrated and is, from a practical standpoint, of com- 

* The active principle of colchicum is without doubt colchicine. See Geiger (Annal. Chem. 
Pharm., vii. 274), Hoppe, Aschoff (Vierteljahresschrift f. Prakt. Pharm., vi.), Schroft (pester. Zeit- 
tchrift f. Prakt. Heilk., 1856), and Albers (Deutsche Klinik, 1856, xxxvi.). Jacobi affirms that abso- 
lutely pure colchicine is physiologically inert, but that it is transformed in the system into a brown, 
amorphous, oxidation product, oxydicolchicine, which produces the poisoning symptoms commonly 
attributed to colchicine. 

Colchiceine is a neutral crystallizable substance, soluble in water, which is produced by the 
action of mineral acids and certain other agencies upon colchicine. Its toxic influence has been 
studied upon dogs by Samuel R. Percy (Amer. Med. Times, April, 1862, 167), according to whom 
it produced symptoms very similar to those caused by colchicine; they are — increase in the fre- 
quency of the pulse, severe purging with tenesmus, vomiting, finally great slowing of the pulse and 
failure of the heart's action, and death without convulsions. The urine, at first increased, was 
afterwards suppressed. On post-mortem examination, the mucous membrane of the intestines was 
found highly inflamed, that of the stomach slightly so, and the heart and arteries were filled with 
black tarry blood, similar to that of colchicine-poisoning. On the other hand, Paschkis asserts that 
one and a half grains of colchiceine injected into the jugular vein of a dog produced no results 
whatever. It is evident that the two experimenters had different substances. Ferrer (University 
Med. Mag.) found that colchiceine acts chiefly upon the motor, and not, as does colchicine, upon the 
sensory nerves, and that while it stimulates the peripheral vagi, it does not depress the heart-muscle. 
S, R. Percy affirms that in gout colchiceine increases the elimination of urea and of uric acid, 
but his experiments are too few to be decisive. 



392 GENERAL REMEDIES 

paratively little interest. According to both Rossbach, and Adolfo 
Ferrer y Leon, it has very little action upon the circulation, although 
Schaitanoff and Paschkis state that the drug notably increases the 
arterial pressure. It has a distinct depressant action upon the nerv- 
ous system affecting especially the sensory nerves, and to a lesser 
extent also the spinal cord. Dixon states that it causes a marked 
leucocytosis. Kionka asserts that colchicine causes a marked increase 
in the secretion of bile. 

Upon most animals toxic doses of colchicum acts very much as it does upon 
man, in poisonous doses producing, as prominent symptoms, severe and often bloody 
purging, vomiting, great prostration, embarrassed respiration, finally more or less 
pronounced paralysis, and death, not rarely preceded by convulsions. Reflex actions 
are lessened and finally abolished (Albers, Rossbach) in the frog; but Rossbach 
affirms that there is a precedent stage of convulsions with excessive reflex activity; 
in warm-blooded animals this first stage of excitement is rarely, if ever, seen. 

The force of the poison is chiefly expended upon the alimentary 
canal, which is always found, at least in mammals, to be in a condi- 
tion of intense inflammation, even when colchicine has been given 
hypodermically. 

The relief which is afforded in a gouty condition by purgative 
doses of colchicum can hardly be explained by the supposition that the 
drug causes the elimination of gout-poisons through the bowels, because 
the effects produced by doses too minute to act upon the gastro- 
intestinal tract are often decisive; so that great interest attaches 
to the question as to the influence of the drug upon the kidneys. 
It is certain that sometimes the continuous moderate use of colchicum 
distinctly increases the flow of urine, but its action is not invariable, 
and, unfortunately, the question as to whether the drug notably 
increases the elimination of solid materials from the urine cannot at 
present be answered with definiteness, the testimony in regard to 
the action of colchicum upon the elimination of urea and uric acid 
in health and in disease being too contradictory and insufficient to 
warrant any conclusion. 

Thus, Bird quotes Krahmer's experiments as showing that colchicum does not 
increase the amount of solids eliminated in health, and intimates that his own 
investigations had given similar results; while Hammond, on the other hand, in a 
series of experiments in which every care to avoid fallacies, by maintaining equality 
as to diet and exercise, was observed, found that while squill and digitalis increased 
only the watery part of the urine, both the organic and the inorganic solids were 
remarkably augmented by colchicum. 

The testimony as to the effects of the drug in disease is no less discordant. In 
1828 Chelius announced that during its administration in gout the amount of uric 
acid eliminated is nearly doubled. R. Lewins submitted the urine of several per- 
sons suffering from gout, taken before and after the administration of colchicum, 
to Christison, who found in the colchicum-urine the proportion of urea nearly double, 
and that of uric acid greater than, that of the other specimens. 

In 1852 Maclagan analyzed the urine of three cases of rheumatism before and 
after the exhibition of colchicum: in two instances the proportion of urea was very 
greatly increased, that of uric acid slightly so. In the third case the effect just noted 
happened at first, but not afterwards. 



ALTERATIVES 398 

On the other hand, Stille" states thai (haves and Gardner affirm that the mates 
diminish under the use of tlie medicine. It is evident thai these different results are 

not so contradictory as they seem, for it is possible that in one case the eolehiemn 
may so art as to increase the elimination of urea, in another thai of uric acid, and 
that when one of these is increased the other may lie unaffected, ore\en diminished. 
Further, when the medicine purges freely it is very probable that elimination 
by the kidneys is lessened; and no account of this is taken by any of the observers 
whose original papers we have seen. Moreover, these observers also all contented 
themselves with noting the proportion of urea and uric acid in the urine, when it is 
evident that the mere proportion, unchecked by the absolute amount of urine 
secret ei I during the twenty-four hours, is no criterion as to the absolute amount elim- 
inated. A. B. Garrod has made a study of the subject in such a way as to avoid 
this fallacy, ami found that the elimination of urea and uric acid Wits sometimes 
increased, but that, on the whole, no marked effect was produced. Noel Pattern 
states that in his experiments on dogs small doses of COlchicum increased very dis- 
tinctly the elimination of urea and uric acid, as well as the amount of the urine; 
while large doses lessened the amount of urinary secretion and increased slightly 
the daily elimination of urea and uric acid. He believes that the increase was due 
to an increased production, because after the administration of the drug the daily 
elimination did not fall below the normal. We do not think, however, that at present 
we are warranted in considering it established that colehicuin materially influences 
nitrogenous elimination. 

Therapeutics. — Colchicum is of no value in practical medicine 
save for the treatment of gout, in which disease it has long been recog- 
nized as a specific. Our acquaintance with its physiological action is 
not sufficiently positive to establish any theory as to the method in 
which the drug acts. It may be that it simply increases the throwing 
off of gout-poisons, but this is not proved. The theory advocated by 
Hugo Schulz, that it increases very greatly the circulation in the 
capillaries of the muscles and joints, and thereby brings relief in gouty 
states of passive congestion, and causes absorption of gouty exudates, 
is ingenious, and may or may not be true. 

Colchicum may be used to prevent the coming on of a gouty par- 
oxysm, or to lessen the severity of the symptoms when the paroxysm 
has already been developed. During an attack of gout, from three 
to five minims (0.2-0.3 C.c.) of the fluidextract of colchicum seed 
may be exhibited every four hours until some decided evidence of 
its action, such as nausea or slight purging, is induced. It should 
always be borne in mind that although looseness of the bowels may 
be useful, yet severe purging is to be avoided. In some cases, espec- 
ially in debilitated subjects, the action of the drug upon the bowels 
should be restrained by the use of opium or other medicament. By 
large purgative doses of colchicum the paroxysms of gout may often 
be suppressed; but experience has shown that this use of colchicum 
is dangerous, the suppression being sometimes followed by serious 
internal disease, apparently due to a transfer of the gouty irritation. 
Between the paroxysms colchicum may steadily be exhibited to the 
gouty subject in small doses, and often great advantage is derived 
from its combination with potassium iodide. 

In rheumatism colchicum has been highly recommended, but is of 
little value. Colchicum has been administered in various diseases, but 
when there is no rheumatic or gouty taint is at present very rarely used. 



394 GENERAL REMEDIES 

Toxicology. — In poisonous doses colchicum produces violent 
purging, whose onset is soon followed by severe, often uncontrollable, 
vomiting. The discharges from the bowels are at first large and 
serous, but later become smaller, more mucous, with flaky deposits, 
and finally in some cases bloody. Abdominal pain may be absent 
or present, but if present is generally griping; sometimes there is 
gastric burning. Nervous symptoms have been prominent in some 
of the severe cases. In one instance, it is said, a feeling of numbness 
or prickling was complained of by the patient; but this seems not 
to be common. Spasms are very frequent, and sometimes convulsions, 
which may be fatal, are present. Muscular pains are not rarely experi- 
enced: in some cases replacing the spasms, and probably in all other 
cases coincident with them, is great muscular weakness, amounting, 
as death approaches, to paralysis. Finally, a condition of collapse 
develops, the circulation fails more and more, the pulse, which has 
been frequent and feeble, becomes rapid and thready, the skin cold, 
pale, or livid, and bedewed with sweat, and death from exhaustion 
results. Consciousness is preserved until the last. The effect of 
lethal doses of colchicum on the urinary secretion varies: sometimes 
the kidneys seem to be nearly unaffected almost to the last: sometimes 
their functional activity is decidedly increased, but in other cases it 
is diminished, and even suppression of urine has been noted. 

After death from colchicum the blood is generally found very 
dark and imperfectly coagulable, but whether this is due to a direct 
action of the poison or is the result of the slow death by asphyxia 
and exhaustion has not been determined. The chief changes are, 
however, in the alimentary canal, the mucous membrane of which 
is much swollen, intensely congested, sometimes ecchymotic, or with 
blood free in the intestine. 

As was first pointed out by Schroff, and since confirmed by Rossbach, the 
rapidity of death in colchicine-poisoning is not at all in proportion to the size of the 
dose. Thus, Schroff noticed that one and a half grains of colchicine produced death 
in the rabbit in fourteen hours, while fifteen grains killed in eleven hours. This 
failure of relation seems to be explicable only by the supposition that colchicine 
kills chiefly by its irritant action on the alimentary canal, and, not being in any dose 
corrosive, requires time to work out the fatal result, through the instrumentality of 
a gastro-enteritis. This deduction is confirmed by the long-protracted course of 
the poisoning after small doses. Thus, Aschoff noted death on the ninth day in a 
pigeon which had received one-fourth of a grain of the alkaloid. 

The fatal dose varies, but is small. George B. Wood states that 
death has been produced by two drachms and a half of the wine of 
colchicum root, and Taylor records a case in which three drachms 
and a half proved fatal. On the other hand, recovery has taken 
place after the ingestion of an ounce.* According to the experiments 
of Schroff, colchicine is eighty to one hundred times stronger than 
the fresh corm. According to Heinrich (quoted by Husemann), 

* See case in L'Union Medicate, Aug. 1848. 



ALTERATIVES 39fi 

0.15 .main of colchicine will produce poisonous symptoms in man, and 
in Krahmer's experiments o.;} grain caused in an adult violent serous 
purging, lasting for four days, and accompanied by severe tenesmus. 
Casper has seen death result from a quantity of the wine containing 
0.025 to 0.03 gramme (0.37-0.45 grain) of colchicine; but, according 
to Eusemann, recovery has taken place after the ingestion of 0.045 
gramme of the alkaloid.* Suffet and Faastem report death in a case 
of nephritis from 0.003 gramme of colchicine dissolved in 2.40 
grammes of methyl salicylate. 

The treatment of colchicum-poisoning is as follows. If the stomach 
and bowels have not been freely evacuated, administer at once an 
emetic and a cathartic, so as to empty the alimentary canal; allow 
the patient to drink freely of warm water, to aid in these operations 
and to act on the kidneys. Give freely of tannic acid, as the only 
known chemical antidote, although experiments upon animals have 
shown that it is not to be relied upon. To check the vomiting and 
purging, administer opium freely; and to allay the irritation, cause the 
patient to drink freely of albuminous matter, such as white of egg 
dissolved in water: the tannic acid having been given as soon as pos- 
sible after the taking of the poison, the demulcents are useful in the 
more advanced stages. Symptoms of gastro-enteritis or of collapse 
are to be met as they arise. 

ICHTHYOL. 

Ichthyol is a substance first prepared by Schroeter by the distilla- 
tion of a peculiar bituminous sulphurous mineral obtained from the 
deposits of fossil fish. It occurs in commerce in the form of sodium 
ichthyo-sulphate and ammonium ichthyo-sulphate. Ammonium ich- 
thyol is a reddish-brown, clear, thick liquid, of a hot bituminous taste 
and smell, at a high heat burning without ash, making with water a 
clear, reddish-brown solution of a weak acid reaction, which, when 
treated with hydrochloric acid, yields a dark resinous precipitate. 
Sodium ichthyol is a dark, tar-like substance of an alkaline reaction, 
perfectly soluble in water. Both these preparations combine with 
fat and vaseline in all proportions. The ichthyol preparations are 
said to contain ten per cent, of sulphur. 

Therapeutics. — According to Baumann and Schotten, ichthyol 
has little apparent action on the general system, and when given to 
dogs in doses of five drachms produces no symptoms save diarrhoea. 
As a local remedy it has been extravagantly praised by Unna, Kiesner, 
and a large number of German dermatologists and surgeons, and has 
also received strong encomiums in America. When applied freely 
in a pure form to the sound skin it produces slight irritation and 

t George W. Major (Canada Med. and Surg. Journ., Dec. 1873) records seventeen cases of 
poisoning from one bottle of wine of colchicum seeds, occurring in Montreal, seven of which proved 
Fatal. The patients had been vomiting and purging almost continuously for many hour* when 
first seen, and the symptoms were exactly those of the stage of collapse of severe cholera morbus. 
In no case was the purging bloody. Consciousness was preserved to the last, and in only one case 
was there anything like convulsions. There was decided numbness of the extremities, and a peculiar 
hoarseness of the voice was especially noted. 



396 GENERAL REMEDIES 

burning. It is asserted to have, when used as a local application, 
peculiar alterative properties, and also the power of penetrating 
through the skin so as to be able to act as an alterative anodyne and 
discutient in diseases not only of the skin but also of the subja- 
cent tissues, probably having also germicidal powers. The cases in 
which it is of value are characterized generally by inflammatory 
enlargement or inflammatory pain. 

In various skin diseases ichthyol has been used with alleged 
remarkable results, — in chronic eczema, chronic urticaria, acne, inter- 
trigo, lupus, keloid, etc. In lepra Unna combines its internal and 
external use (dose, fifteen grains (1 Gm.) a day). It has also been 
recommended in the strongest terms for the relief of various ulcera- 
tions of the skin and for the prevention of pitting in small-pox, and 
also in erysipelas. In lumbago and other forms of muscular rheumatism, 
in rheumatic or gouty joint disease, indeed, in almost every form of 
subacute or chronic gout, according to Schweninger, Lorenz, and 
others, a few rubbings with pure ichthyol or a fifty per cent, ointment 
will produce an immediate and remarkable effect. It has been largely 
used in the treatment of sprains, contusions, burns, and frost-bites. 
If one-half that has been said of it be true, it is a local remedy of 
extraordinary power and value. Schmidt has even seen it soften 
and disperse a lipoma, and D. Hayes Agnew commends it very highly 
in the treatment of recent lymphatic enlargements. In sprains, when 
the skin is intact and not irritated, the ichthyol itself or a fifty per 
cent, ointment may be employed. In erysipelas Von Nussbaum covers 
the affected part, after thorough disinfection, with a thick layer of 
equal parts of ichthyol and petrolatum, and this in turn with a thick 
layer of salicylated cotton. The result is said to be immediate, the 
disease disappearing in a single day. In various skin diseases and 
ulcerations the strength of the application may vary from one to 
fifty per cent. Lorenz affirms that in acute coryza and inflammations 
of the nose or mouth a mixture of one to ten per cent, of ichthyol 
and petrolatum is very efficacious. Both Unna and Lorenz deny that it 
has any antiseptic properties. 

Ichthyol Albuminate. — Ichthalbin is a greenish-brown powder, 
made by precipitating albumin with ichthyol, and containing sevent}'- 
five per cent, of ichthyol. It is insoluble in water, but soluble in 
alkaline solutions; it is odorless, almost tasteless, and has been highly 
praised in syphilis and in scrofulous conditions with lowered general 
nutrition. Dose, fifteen to thirty grains (1-2 Gm.) three times a day. 

Isarol, or Ichthyodin, made from crude ichthyol by the action of sulphuric 
acid, is said to contain about nine per cent, of sulphur, to be soluble in water and 
alcohol, and to be therapeutically equivalent to ichthyol. It has been commended 
as a substitute for refined ichthyol on account of cheapness. 

Sarsaparilla. — The roots of various species of Smilax inhabiting Mexico 
and northern South America have long been used in the treatment of chronic syphilis 
and chronic scrofulas. They contain three active glucosides belonging to the sap- 
onin group, namely, parillin, of Palotta; saponin, of Otten; sarsaponin, of Schulz. 



ALTERATIVES 897 

to these glucosides, separate or combined, various names have been given by vari 
one investigators, such as amilacin, talsvparin, tarsajnriUin, and sarUlinic add. < >i 
these glucosides, according t<> Kobert, Barsaponin is the most important, being the 
most active poison to the red blood-diaka known. Palotta found thai in doses of 
thirteen grains parillin causes vomiting and oirculatory depression, but Bflcker was 
unable to obtain Buch results, anil there is n<> reason for supposing that the amounl 
of these saponins in sarsaparilla is sufficient to give to the drug therapeutic activity. 

Official Preparations : 

Fluidextractum Sarsaparilhe I fluidraehra ( I < I.e. I. 

Fluidextractum Sarsaparilla' Oompositum i Buidraohm (,i Co.). 

Syrupus Sarsaparillffi Oompoaitus Vehicle. 

Sarsaparilla lias been used chiefly in the advanced Stages of syphilis as an 
adjuvant to the mercurials and iodides, hut its value IS doubt fill, [fit is of service, it 
is in those cases in which the constitution is very much broken down by the disease. 
It is never used in substance; a compound decoction was formerly much employed, 
being modelled after the famous Lisbon diet-think; it is equivalent to the present 
compound fluidextracl diluted. 

t,i mac. Guaiac resin is believed to be diaphoretic and alterative, and has 
been much used in combination with sarsaparilla in chronic syphilis. In subaaitc 
and chronic rheumatism it is often of service. As suggested by William Murrell, 
ten to thirty grains of it (0.6-2 Gm.) may be given in electuary as an antirheumatic 
laxative in tonsillitis anil chronic rheumatism. 

Tinctura Guaiaci (20 per cent.) 1 to 2 fluidraehms (4-8 C.c). 

Tinctura Guaiaci Ammoniata (20 per cent.) ... 1 to 2 fluidraehms (4-8 C.c). 

Mezereum. — The bark of the Daphne Mezereum is said to contain a volatile 
acrid principle and the glucoside dapknin. In overdoses it is an active poison, 
producing, it may l>c, a fatal gastro-intestinal inflammation. In some cases the 
symptoms have been simply collapse, with unconsciousness, and other nervous 
disturbance (case in British Med. Journ., 1882, ii. 521). Internally, mezereum has 
been used in combination with sarsaparilla; externally its ointment, formerly official, 
has been employed as a stimulant dressing to indolent ulcers. 

Fluidextractum Mezerei 1 minim (0.06 C.c). 

Taraxacum. — The root of the common dandelion, Taraxacum officinale, is 
l>eheved to have the property of altering the action of the liver, although no effect 
is to Ik? witnessed from a single dose of the drug, however large, — other, at least, 
than some nausea. Diuretic properties have also been ascribed to taraxacum; 
but the only evidence brought forward to establish this is the vulgar name which 
the plant bears in both English and in French. If taraxacum be useful at all, it is 
in cases of dyspepsia in which there is habitual torpor of the liver, with constipation. 

Fluidextract Taraxaci 2 to 3 fluidraehms (8-11 C.c). 

Extractum Taraxaci 1.5 to 30 grains (1-2 Gm.). 

Stillingia. — Queen's Root. — Stillingia is said by Bichy to contain an alkaloid, 
Btillingine. In overdose stillingia is an emeto-cathartic; it is used to a considerable 
extent as an alterative, especially in the class of cases in which sarsaparilla has 
been employed, often in combination with it. 

Fluidextractum Stillingia? i to 1 fluidrachm (2-1 C.c). 

X vnthoxylum. — Prickly Ash. — The bark of two American species of Xan- 
thoxylum, said to contain berberine and other alkaloids, is believed by various 
practitioners to resemble mezereum remedially, and has l>een especially useful in 



398 GENERAL REMEDIES 

chronic rheumatism. Externally xanthoxylum is sometimes useful as a mild counter- 
irritant; thus, in chronic pelvic diseases, much temporary relief is often obtained 
by a hot pack applied to the lower part of the trunk, made with four ounces of 
fluidextract of xanthoxylum and one ounce of tincture of cayenne pepper to two 
quarts of water. 

Fluidextractum Xanthoxyli J to 1 nuidrachm (2-4 C.c). 

Jambul. — The bark of the Eugenia jambolana, an East Indian tree, lias long 
been used in India as a stomachic astringent in diarrhoea and as a specific in true 
diabetes. Its active principle has not been determined, but appears to be present 
in the bark, in the seeds, and also in the rind of the fruit; neither have we detailed 
knowledge as to the physiological action of the remedy. 

Thomas Christy found that when sufficient diastatic matter was mixed with 
fifty grains of starch to convert forty-five per cent, of the latter in fifty minutes into 
sugar, the addition of twenty-five grains of powdered jambul seeds reduced the 
conversion of the starch eighty-eight per cent. In Binz's experiments, in dogs 
rendered diabetic by phloridzin, according to the method of Von Mehring, the 
exhibition of jambul reduced the excretion of sugar from fifty to ninety per cent, 
without producing any evidences of posioning. 

In human glycosuria jambul is usually without perceptible influence, but in 
some cases (literature and our own experience) its effects are more marked. It 
never produces any disagreeable effects, and from fifteen to forty-five minims (0.9- 
2.8 C.c.) may be given three times a day. Vix found that in doses of ten drachms 
(37 C.c.) a fluidextract made from the rind of the fruit acted efficiently as a diuretic. 

Thiosinamine. Allyl-sulphocarbamide; Allyl-sulpho-urea; Rhodalline. — This 
substance, which is prepared from the oil of mustard, occurs in colorless monoclinic 
or rhombic crystals, of a bitter taste and feeble garlic-like odor. It is moderately 
soluble in water, very soluble in alcohol and ether. It possesses no bactericidal 
properties, and in the doses in which it has been used seems to exert no influence 
whatever upon the general system, except upon the blood-making organs. Several 
hours after its injection the leucocytes in the blood are greatly diminished in number, 
falling according to Hebra, in some cases from fourteen thousand to four thousand. 
This condition lasts, however, but a short time, and is followed by a pronounced 
hyperleucocytosis. During the latter period a very pronounced destruction and 
absorption of exudates and of cicatricial and other poorly nourished tissues are 
said to occur. 

Thiosinamine was introduced into medicine by Von Hebra for the treatment 
of lupus and old cicatrices and has been used by many clinicians in lupus, chronic 
glandular inflammations, scleroderma, keloid, urethral strictures, corneal opacities, 
plastic iritis (G. F. Suker), and sclerotic conditions of the ear with consequent 
deafness. Una has also employed it locally in the form of a five to twenty per 
cent, soap or plaster in fibrous tumors, keloid, leprous, and syphilitic lesions, and for 
small-pox scars. Its local application may be continued for some hours, and is said 
not to produce irritation or pain. George E. de Schweinitz informs us that very 
extensive trials have forced him to the conclusion that the internal administration 
of thiosinamine is of no value whatever in any disease of the eye. 

Dose, in capsule, one-half to three grains (0.03-0.2 Gm.); hypodermically, one 
to four grains in ten to fifteen per cent, alcoholic solution, preferably injected into 
the intracapsular or gluteal region; or, when the disease is superficial, in the neigh- 
borhood of the lesion. Considerable pain is said to be produced by the injection. 

LECITHIN. 

Lecithin is a complex fatty body representing the phosphorus-holding molecule 
of the central nervous system. It occurs, however, not only in the higher animals 
but in many of the food-stuffs, and is especially abundant in embryonal tissues, as 
eggs and seeds. There are several varieties of lecithin so that the lecithin of eggs, 



ALTERATIVES 399 

for example, is not chemically the same as that found in the human nervous system. 

The human lecithin is a di-xtcaryl-yh/ccrophosphutc of rlwlin, but any oilier laity 
acid as oleic or palmitic, may ho substituted for the stearic; thus we may have a 
palmityl or an olevl lecithin. It is not probable that there is any marked difference 

in the physiological properties of the different forms of lecithin. 

Lecithin occurs as a yellowish, waxlike substance, soluble in ether and alcohol. 
In water it swells up and forms a sort of emulsion but strictly speaking is 
not dissolved. 

Physiological Action. — It has been shown by H. C. Wood, Jr., that 
lecithin is non-toxic, and, unless injected in enormous quantities, has practically 
no immediate physiological action. Amounts equivalent to 0.2 gramme per kilo 
somewhat slow the respiration and pulse, but do not materially alter the 
blood-pressure. 

Lecithin is unstable and easily decomposed into its component parts, one of 
which, choline, is poisonous. Choline is closely related to the actively toxic sub- 
stance, neurine. These poisonous principles seem to be in the nature of alkaloids. 
Their toxic effects consist principally in paralysis of the respiration, of the peripheral 
motor nerves and of the spinal cord, stimulation of the peripheral ends of the pneu- 
mogastric nerve, and temporary rise of the blood-pressure followed by a fall, which 
with toxic doses brings it below normal. 

Danilewsky found that pups, to which were administered lecitliin, increased 
in weight more rapidly than did the control animals, and that there was an augmen- 
tation in the number of red blood-cells without, however, a corresponding increase 
in the percentage of hemoglobin. Serono obtained a similar result in studies made 
upon human beings, and also determined greater elimination of urea, despite which 
fact there was a gain in weight. This increase in the weight is probably attributable, 
as Serono points out, to a stimulation in cellular reproduction brought about through 
the excess of protoplasmic phosphorus in the parent cell. 

Therapeutics. — Claude and Zaky and Gilbert and Foumier have employed 
lecithin in tuberculosis, with resulting gain in weight. Serono finds it of some value 
in chlorosis, but less active than the iron salts. Lancereaux and Paulesco employed 
it in two cases of pancreatic diabetes with gain in weight and diminution in the 
amount of sugar. The dose is from 0.1-0.3 gramme (1-5 grains). It was at first 
used hypodermically because of the fear that it would be broken up by the digestive 
juices into its component parts the remedial effect of which is very doubtful. Danil- 
ewsky and Gilbert and Fournier assert, however, that it acts when given by the 
mouth as well as when given hypodermically, although it must be administered in 
larger doses. 

GELATIN. 

Gelatin is an albuminoid body derived from fibrous and carti- 
laginous tissues. Its use in medicine depends on its power of increas- 
ing the coagulability of the blood, as was first shown by Dastre and 
Floresco. 

Physiological Action. — Absorption and Elimination. — The orig- 
inal results of Dastre and Floresco were obtained from the intraven- 
ous injection of gelatin. It has been, however, since then abundantly 
shown that the drug is capable of acting after hypodermic injections, 
and it must be absorbed, therefore, from the subcutaneous tissues. 
Camus and Gley assert that the subcutaneous injection of gelatin 
can have no effect on the coagulability of the blood, because, being 
an undialyzable substance, it is incapable of absorption. They 
found experimentally that the introduction of gelatin into the peri- 
toneal cavity did not increase the coagulability of the blood, and two 
hours after the injection a large portion of the gelatin solution still 



400 GENERAL REMEDIES 

remained in the peritoneal cavity. Lancereaux and Paulesco deny 
the correctness of the conclusions of Camus and Gley, claiming that 
subcutaneous injection of gelatin is equivalent to injecting it directly 
into the lymph channels, whence it may be taken up whether dialyz- 
able or not, pointing out as analogous the fact that ascitic fluid, which 
is equally undialyzable, is frequently absorbed. They found, further, 
that the intraperitoneal injection of gelatin does increase the coagul- 
ability of the blood, and that the solution introduced disappears 
from the abdominal cavity. 

Concerning the question of its absorption from the intestinal 
tract there has been considerable dispute. It is impossible that 
gelatin can be absorbed by mucous membranes unchanged, since 
being an albuminoid it is not dialyzable. Many substances, however, 
are capable of producing changes in the physical properties of gelatin. 
Thus it has been shown by the experiments of Dastre and Floresco 
that if maintained at a temperature of even 110° C. for a long period 
of time it loses the property of jellying; strong solutions of the iodides 
and chlorides also destroy the property of solidifying. These changes 
are probably similar to those which take place in the digestion of this 
substance. The digestion of albuminoids such as gelatin is similar 
to that of the true albumins; that is, the albuminoid is converted 
by peptic digestion first into a substance allied to the albumoses, 
known as gelatose, and later into a substance known as gelatin- 
peptone, all of these derivatives being soluble in water at ordinary 
temperatures. According to the experiments of H. C. Wood, Jr., 
these substances, arising from the digestion of gelatin, like the gelatin 
itself, increase distinctly the coagulability of the blood, and being 
dialyzable are easily absorbed. These results seem to indicate clearly 
that gelatin given by the mouth and being digested is capable of 
influencing the clotting of the blood. And despite the contrary 
opinions of several authors, there can be to-day little doubt but that 
gelatin acts when given by the stomach. 

From the experiments of Dastre and Floresco it would seem prob- 
able that the gelatin introduced intravenously was eliminated largely 
unchanged, since these authors found that the urine of a dog so 
treated solidified on cooling. 

It has been claimed that in its passage through the kidneys gelatin 
acts as a local irritant, and Freudweiller and others have asserted 
that in cases of hematuria it increases rather than diminishes the 
amount of bleeding from the kidney. On the other hand, Lutkens 
found that it had no deleterious action in experimental nephritis in 
rabbits. Schwabe, Hahn, and many other authors have found that 
bleeding from the kidney was cured by the drug. 

That the coagulum produced by gelatin is a true clot, and not as 
was by some believed, a jelly, is shown by the following facts: The 
process of clotting takes place at the temperature of 38° C, at which 
temperature gelatin will not jellify, and gelatose, which does not 
jellify at all, causes the blood to clot in about one-third the normal 



ALTERATIVES 401 

time. Further, it was found by Dastre and Floresco that apparently 
the gelatin does not enter into the composition of the clot, since 
the serum which is expressed from the clot is capable of solidifying 
on cooling, showing that at least it contains a considerable proportion 
of the injected gelatin. 

There has liocn considerable discussion as to the cause of this increase in the 
coagulability of the blood. Zibell believes that it is due to the contained lime. 
This, however, seems extremely improbable, for according to his own experiments 
the proportion of lime present is only six-tenths of one per cent., and one gramme of 
gelatin representing only 0.00(5 gramme of lime is capable of distinctly increasing 
the rapidity of coagulation. Dastre and Floresco assert, moreover, that gelatin is 
not capable of overcoming the delayed coagulation produced by decalcification of 
the oxalic acid, but that it is capable of overcoming the anti-coagulant effect of 
peptone. Edsall believes that the increase in the rate of clotting depends upon the 
more rapid destruction of the red blood-corpuscles. Moll claims to have shown 
that gelatin increases the fibrinogen and has an agglutinizing effect on the red 
corpuscles. 

In discussions concerning the cause of the gelatin clot, investi- 
gators have curiously overlooked a fact known for a long time, namely, 
that gelatin is not alone in its effect upon the coagulability of the 
blood. Various albuminoid bodies likewise accelerate coagulation. 

Therapeutics. — Gelatin has been employed in nearly all forms 
of bleeding, whether internal or external; thus, for example, in 
cpistaxis, hematemesis, and other local hemorrhages its topical appli- 
cation is valuable. Internally it has given good results in hemop- 
tysis, hematuria, purpura hemorrhagica, hemophilia, and the like. 
Kehr has found it useful for staunching the hemorrhage following 
operations on the biliary system. Lemoine has found it useful to 
check the bleeding following leech-bites. Manicotide and Christo- 
dulo, and Bertimo-Besdetnoff, recommend its use as a local appli- 
cation to the uterus in menorrhagia, metrorrhagia, and other uterine 
hemorrhages. 

Gelatin has also been employed in the treatment of inoperable 
aneurism, and appears to be of value when the aneurism is sacculated 
(see Lancereaux.) 

Administration. — The intravenous injection of gelatin, we 
believe, is absolutely unjustifiable, on account of the very imminent 
danger of the formation of thrombi. In cases where an immediate 
action is not necessary, we believe that the administration of gelatin 
by the mouth is the best method, since it avoids the danger of infec- 
tion, allows of frequently repeated doses, and is probably equally 
efficient. We have seen hemoptysis and long-standing menorrhagia 
controlled immediately by the use of gelatin by the mouth. Rocchi 
recommends the administration of gelatin through the rectum. The 
dose we have employed by the mouth represents from one to four 
drachms of the dry gelatin three or four times daily. This may be 
given preferably in the form of a ten-per-cent. jelly, which may be 
flavored to taste. It must be remembered in this connection that 
the ordinary gelatin as prepared for culinary purposes contains 
26 



402 GENERAL REMEDIES 

only three or four per cent, of gelatin itself, and must be used in 
correspondingly large quantities to have any effect. 

In those cases of severe hemorrhage where immediate control of 
the bleeding is necessary and where local application is not practic- 
able, recourse may be had to the hypodermic administration. Under 
these circumstances the gelatin should be given in warm solutions 
of from two to five per cent, in normal saline, of which from one 
hundred to two hundred c.c. (3-6 fluidounces) may be given at a 
dose. The technic for these injections is precisely the same as that 
employed for hypodermoclysis. Great care must be taken in the 
preparation of these solutions, as in a large number of cases not only 
pyogenic infection but fatally ending tetanus have been reported 
from the hypodermic use of gelatin. According to Dorfler even 
repeated boiling does not render the solution absolutely free from 
danger, since even if bacteria are killed certain toxins may not be 
destroyed. The patient may thus die of tetanus, although no germs 
are introduced. For hypodermic administration there have been 
placed upon the market sterilized solutions of gelatin, which are 
tested upon guinea-pigs and guaranteed to be sterile and free from 
toxin. t These solutions are preferable, but should be sterilized by 
boiling for twenty minutes immediately before using. The prolonged 
boiling does not change the coagulating effect of the drug on the blood. 
Locally gelatin may be applied by means of a tampon saturated with 
hot ten-per-cent. solution. The glycerinated gelatin (Gelatinum 
Glycerinatum,) occurs in pieces and contains about fifty per cent, 
of gelatin. 

Nuclein. — An organic remedy whose value is very problematical 
is the so-called nuclein. Originally the term nuclein was applied to 
a peculiar phosphorized substance isolated from the nuclei of pus- 
cells. Later clinical research has shown that there are in nature 
numerous closely allied, phosphorized, proteid-like bodies to which 
the name may be applied, and which have been shown by Kossel and 
his co-workers to be a combination of nucleic or nucleinic acid with 
a proteid body. Nuclein on a large scale is preferably prepared from 
the yeast-cell, and readily yields nucleic acid, an amorphous white 
powder of strong acid reaction, readily soluble in alkalized water, 
containing as much as nine per cent, of phosphorus, but, according 
to Chittenden, no proteid matter. It occasionally exists free in animal 
cells as in spermatozoids, but is generally united with a proteid. 
Nuclein is furnished to commerce especially in the form of a five-per- 
cent, solution, of which the dose is from ten to sixty minims hypo- 
dermically. It is alleged that it is a powerful germicide, and so slightly 
toxic that it has been injected intravenously by Vaughan and McClin- 
tock until the blood of the animal contained one and one-eighth 
per cent, of pure nucleic acid without serious results. It has been 
especially commended in the treatment of tuberculosis, puerperal 
fever, and other germ diseases. 



ALTERATIVES 403 

THYROID BODY. 

The exact function of the thyroid body is not definitely known; 
the removal of it causes death in both dog and man. In the dog the 
lethal result takes place in the midst of tetanoid symptoms, death 
occurring usually during a convulsion. In man its absence, congenital 
or operative, produces the disease known as myxosdema, first described 
by (3rd. The symptoms of this disease are increasing weakness 
associated with swelling of the body, enlargement and thickening of 
the skin, mucoid exudation into the subcellular tissue, and a very 
extraordinary slowing of all functions. The appetite is feeble, the 
movements are slow, the temperature is subnormal, and the patient 
thinks with great slowness; as the days go on the universal slowing 
of function becomes more and more marked until the subject sinks 
into a condition of complete apathy with very much lowered 
temperature and a failure of all vital activities. 

Baumann isolated from the thyroid gland a proteid substance 
containing iodine, which he asserted to be the active principle of the 
body. The activities of this substance, which is variously known as 
thyroiodin or iodothyrin, have been called in question by Gottlieb 
and Wormser, who state that it is incapable of stopping the progress 
of symptoms caused by thyroidectomy. But the contrary results 
achieved by E. Roos, Arthur Hennig, Truebel, Ewall, E. Levy Hilde- 
brandt, and Baumann and Goldmann, seem to confirm the claims of 
Baumann; and even if the substance be not the sole active principle 
of the gland, much therapeutic virtue must be conceded to it. Thy- 
reoantitoxin, which was described by Frankel, contains no iodine, 
and appears not to be active (Roos); a statement which is also true 
of the principle separated by Dreschsel. (See Robert Hutchinson.) 
It would appear probable from the various researches that iodo- 
thyrin is the chief active principle of the thyroid body, but that there 
is also in the gland a second substance which has physiological activity. 

Physiological Action. — In elaborate experiments of G. Ballet 
and E. Enriquez upon dogs it was found that half an hour to two 
hours after the ingestion of a full meal of the sheep's thyroid there 
was usually elevation of temperature, with great increase of the 
pulse-rate, though in some cases the tachycardia alone developed. 
Rarely there were general excitement with paroxysms of violent 
tremblings and dyspnoea. The subcutaneous injection of the extract 
of the thyroid caused immediate fever, tachycardia, crises of tremb- 
ling and dyspnoea, extreme agitation, and in two cases distinct 
exophthalmos. Continuous thyroid-feeding produced conjunctivitis, 
general wasting, and derangement of the digestion, but in no case 
death. On the other hand, repeated hypodermic injections of the 
extract led to rapid emaciation, paroxysms of violent diarrhoea and 
melanemia, sometimes polyuria, sometimes albuminuria, with great 
weakness of the hind legs, occasionally amounting to paralysis, 
followed by torpor, collapse, and death. Tumefaction of the thyroid 



404 GENERAL REMEDIES 

lobes was noted in some cases during life, and after death the thyroid 
body was found to be greatly enlarged and mottled with ecchymoses. 
By microscopic examination there were revealed marked evidences 
of inflammatory change in the thyroid gland, with destruction of the 
alveolar and epithelial cells and the development of sclerotic tissue. 

In man thyroidismus, so called, has been developed in a number 
of cases by the excessive administration of the gland. The chief 
symptoms are progressive loss of weight, shortness of breath, weak, 
rapid pulse, and general nervousness. 

As the result of his own experiments, Hertoghe asserts that the 
thyroid extract lessens the activity of the pelvic organs of women, 
while it stimulates the thoracic genital organs, so that it causes arrest 
of menstruation but increases the secretion of milk. 

According to Ott, the drug depresses reflex action in the frog. 

Circulation. — Vamossy and Vas state that the intravenous injec- 
tion of iodothyrin has no effect on pulse-rate, blood-pressure, or 
respiration, and attribute the symptoms seen after its ingestion 
entirely to disturbances of metabolism. But Haskovec, Oliver and 
Schafer, and Ott agree that the thyroid extract causes a slight fall 
of pressure, with some increase in pulse-rate. According to Has- 
kovec the fall of the pressure is due to depression of the heart muscle, 
while the increased pulse-rate is brought about by accelerator 
stimulation.* 

Respiration. — Ott found the respiratory rate increased in the rabbit 
by iodothyrin. 

Blood. — According to Vamossy and Vas, and Bell, the thyroid 
extract has practically no effect on the red blood-corpuscles or hemo- 
globin. M. L. Perry found, as the result of thyroid-feeding in the 
insane, no change in the number of the white blood-corpuscles, but 
a marked lessening of the percentage of the multinuclear and a corre- 
sponding increase of the mononuclear leucocytes, results which agree 
substantially with those of Mosely, save that the latter found some 
lessening in the total number of white corpuscles. Bell and Vamossy 
and Vas, on the other hand, found an increase in the number of 
leucocytes brought about by the thyroid body. 

Nutrition. — Although Scholz, Richter, and Paul Mayer, failed to 
get evidences of increased nitrogenous elimination over intake, 
nevertheless, the concordant results of Roos, Gluzinski and Lim- 
berger, David, Schondorff, Napier, Mendel, Ord, and others, leave 
no room for doubt that there is an increase in the destruction of 
proteid substances brought about by the continued administration 
of the thyroid. Roos found that there is not only an increase in the 
excretion of nitrogen but also in phosphorus and chlorides. Irsai, 
Vas and Gara have shown that these facts hold true in goitrous, 
and Vermehren in myxcedematous, subjects. 



vagus 



The claim of Cyon (.4. G. P., 189S, 77, 42) that iodothyrin will restore tone (o an atropinized 
has been disproven by Femgvessy (II". A'. W., 1900, xiii. 125.) 



ALTERATIVES 405 

But the loss of weighl is not entirely due to the destruction of 

albuminous tissues. Thus, in Schondorff's experiments, out of 2.2 
kilos lost in a three weeks' experiment, there was only sufficient 
increase of nitrogen excreted to account for one kilo of bodily tissues. 
Bleibtreu and Vendelstadt attribute only one-sixth of the weight- 
loss to the breaking down of the proteids. The conclusion seems, 
therefore, inevitable that there must be under the influence of thy- 
roid-feeding not only increased katabolism of proteid, but also of 
fatty tissues. This conclusion is confirmed by the results of Magnus- 
Levy, who found an increase in the absorption of oxygen and giving 
off of C0 3 brought about by thyroiodin. In myxcedematous subjects 
the increase in the demand for oxygen may amount to ninety per 
cent. Magnus-Levy found Frankel's thyreoantitoxin to be without 
effect on the exchange of gases. Schondorff states that the destruc- 
tion of nitrogenous tissues does not begin until the store of reserve 
fat is exhausted. 

Bettmann and W. D. James report glycosuria following free use 
of the thyroid extract. Porges has found in the dog that the excre- 
tion of sugar may persist for weeks after the withdrawal of the thyroid. 

Therapeutics. — It is evident that a myxcedematous condition 
of the body is the result of the absence from the blood of some prin- 
ciple or principles which are supplied in the normal animals by the 
thyroid gland, and which may be furnished to the blood by feeding 
with thyroid glands. It is further apparent that the myxcedematous 
patient who has been relieved by such artificial supply must relapse 
when the supply is cut off; so that treatment of a myxcedema consists 
of two stages; first, that in which large amounts of the gland are 
administered in order to remove the results which have been produced 
by the lack of the thyroid principle; second, the protracted stage of 
convalescence in which small doses of the gland are given continuously 
in order to prevent the recurrence of the myxcedemic symptoms. 
The most striking results are seen in cretinism or congenital myxce- 
dema. In these a few months treatment with thyroid gland may 
convert a misshapen imbecile into a well-formed child of normal 
intellect. 

The destruction of fatty tissues under its use would seem to render 
the drug of great value in obesity. Unfortunately, however, the 
system soon becomes accustomed to it, and although there is nearly 
always temporary benefit in properly selected cases of obseity, the 
patients are very liable to relapse, even despite the continued use 
of the drug.* 

The diseases in which the thyroid body has been given include 
nearly all the chronic and many of the acute troubles known to hu- 
manity. In some of them it has seemed to be of benefit, but in most 
has proven useless. 

* See Grawitz (Miinchen. Med. Woch.. 1896, 43, 312), Mathieu (Gaz. de H6p., Paris, 1896, 69), 
and Yorke Davies (Brit. Med. Journ., 1894, ii. 42.) 



406 GENERAL REMEDIES 

In various forms of skin disease, especially psoriasis (Bergmann), 
it has been recommended. It has even been asserted to be of value 
in lupus (Gould). 

In mental disturbances, such as melancholia or idiocy, not depend- 
ent on myxcedema, it ma)' be tried, although the reported results 
(Bell, Dobrowsky) are not brilliant, and our own trials have been 
an unbroken series of failures. 

The recorded trials of it by Hertoghe and by Mosely in uterine 
troubles indicate that it may prove of service in menorrhagia, endo- 
metritis, and kindred disorders. Diaballa and Illyes report its use 
in a case of nephritis with increase of the quantity of urine and urea 
and diminution of the amount of albumin. 

Very interesting is the report of R. Lepine of a case of progressive 
myopathy, in which muscles not very badly involved so improved that 
the patient, who had taken sixty grammes a week of the fresh gland, 
returned to his work, refusing to stay longer in the hospital. Murray 
has found it useful in ununited fractures. 

In simple goitre, — the goitre of Switzerland, — before calcareous 
degeneration has taken place, thyroid treatment will often cause 
destruction and absorption of the overgrown gland. The extract has 
been used by J. William White with asserted excellent results in 
bringing about the absorption of large contracting cicatricial masses 
which resembled true keloid. It has been employed in old syphilitic 
and other leg ulcers, and may be cautiously tried in almost all forms 
of disturbed nutrition not attended by a tendency to emaciation. 

In any case the occurrence of symptoms of thyroidism should be 
the signal for the lessening or withdrawal of the dose. In exoph- 
thalmic goitre the extract is a priori contraindicated, the most probable 
explanation of the symptoms of the disease being an excess of the 
thyroid principles in the system, and in several cases in which we have 
tried it it has very distinctly aggravated the symptoms. It would 
also seem to be contraindicated in diabetes mellitus. 

Administration. — The thyroid gland may be given raw or 
very slightly boiled, to the amount of a quarter to half of the gland 
of the sheep daily. The glycerin extract or the dried and powdered 
gland is, however, thoroughly efficient and usually preferable. A 
grain of the dried gland (Glandule Thyeoide^e Sicca:,) may in the 
beginning of the treatment be exhibited three times a day, the dose 
being increased until fifteen or twenty grains (1-1.3 Gm.) a day are 
taken, or some nervousness, shortness of breath, rapid pulse, or other 
physiological symptoms are produced. The dose of iodothyrin is 
about the same as that of the dried gland (fifteen grains). 

Pituitaby Body. — We have very little knowledge of the physio- 
logical value of the hypophysis and almost none of its therapeutic 
value. Its extract causes a marked rise of pressure, which Oliver 
and Schafer attribute to a contraction of the arterioles, and slowing 
of the pulse, which, according to Cyon, is not prevented either by 



ALTERATIVES 407 

section of the vagi or by atropine. Several investigators have failed 
to find pharmacological activity in the hypophysis cerebri. The 
explanation of this discrepancy is offered by the discovery of Howell, 
that the pituitary gland proper is destitute of active properties, the 
stimulant principle residing solely in the infundibular body some- 
times known as the posterior lobe of the hypophysis. Schiff has found 
that the pituitary body causes an increased elimination of phosphates 
without corresponding increase of the nitrogenous elements. 

We know of no condition in which the pituitary body is of 
therapeutic use. Mairet and Bosc have tried it in epilepsy, but 
with no benefit. 

Spleen. — In a case of severe chronic exophthalmic goitre, which 
was under H. C. Wood's care some years ago, an acute splenitis ending 
in abscess developed. In the second or third week of the attack the 
enlarged thyroid body began to diminish, and by the fifth week had 
disappeared. After a protracted and extremely severe illness the 
woman finally recovered from the splenic abscess, and has since 
remained free from any symptoms of exophthalmic goitre. 

In myxcedema, cretinism, etc., it is well known that the spleen 
is frequently enlarged, suggesting that there is some relation between 
this organ and the thyroid body. That the splenic extract is not 
inert is shown by the discovery of Oliver and Schafer, that its intra- 
venous injection in the dog produced a fall, followed by a marked rise, 
in the arterial pressure. 

We have used the splenic extract in various cases of exophthalmic 
goitre, and have found that two practical difficulties attend its admin- 
istration. If it be given by the mouth in sufficiently large doses to 
produce distinct effect it is very apt to cause nausea and sick stomach. 
If it be given hypodermically it frequently causes local abscesses. 
The few trials we have made of it indicate that it is at least worthy of 
being essayed in this intractable disorder. Clark has found the extract 
of spleen useful in cases of insanity dependent on physical exhaustion, 
as in puerperal weakness or anemia. 

ANTITOXINS. 

As a result of growth of pathogenic bacteria in the animal system 
there are produced two substances known as toxins and antitoxins. 
A toxin is a substance produced by the bacterial growth which is 
harmful to the host and generally speaking, therefore, favors the 
growth of the bacteria. The antitoxin is a substance which tends to 
restrict the growth of the bacteria or to neutralize the harmful effects 
of their growth. It appears to be the defensive reaction of the system 
against the bacteria. The therapeutic uses of toxins are considered 
in the article on opsonins (p. 414). 

The mode of action of the antitoxin in infectious diseases has been 
the subject of a large amount of surmise and study, but while a num- 
ber of interesting theories have been suggested, notably that of Ehr- 



408 GENERAL REMEDIES 

lich, it must be confessed that we have no positive knowledge of the 
manner in which this substance acts in infectious diseases. It seems 
probable that the actions of different serums are not the same. If 
antitoxin be given to an animal suffering from an infectious disease 
due to local lodgement of a pathogenic germ, the first evidence of bene- 
ficial action is failure of the germs to grow, though they are not killed. 

Antidiphtheric Serum. (Serum Antidiphthericum) , Diphtheria 
Antitoxin. — The U. S. Pharmacopoeia requires that the antidipheritic 
serum shall be of the standard strength, expressed in units of anti- 
toxic power, established by the U. S. Public Health and Marine 
Hospital Service, and it should always be freshly prepared, as even 
when preserved in the best manner it gradually loses its power, the 
annual loss varying from ten to thirty per cent. Although the abun- 
dant clinical evidence appears to demonstrate beyond all doubt that 
diphtheria antitoxin is an absolute specific in diphtheria, it is essential 
that it be used early, as it acts chiefly by arresting the growth of the 
bacilli. If the antitoxin be given late in the disorder it may arrest 
the further growth of the germ, but the patient may die, neverthe- 
less, because the tisssues are already fatally poisoned with the toxin, 
or, perchance, have already undergone an irreparable degeneration. 
Again, there is in every bad case of diphtheria after the first twenty- 
four hours a general septic infection: so soon as lodgment has been 
fairly effected by the Loftier bacillus, and local tissue-change set in, 
streptococci and other septic germs begin to develop rapidly in the 
dying tissues, and very soon give origin to a general septic infection, 
which is most fatal cases of diphtheria is an important factor in the 
causation of death. Evidently a Loftier bacillus antitoxin is useless 
against a streptococcus toxin. 

The absolute importance of the early use of the antitoxin during 
diphtheria is very evident. There are very few, if any, well-observed 
cases of diphtheria on record in which it has been positively deter- 
mined that the antitoxin, administered during the first few hours 
after the outbreak of the disease, has failed to bring about a cure. 
On the other hand, statistics seem to show that if the injection be 
postponed to the fifth day, the mortality-rate is not reduced by the 
use of antitoxin. Our modern municipal scientific methods, not- 
withstanding all their laudations, are liable to become causes of death. 
A case of suspected diphtheria presents itself to the practitioner; 
already the child has been sick, it may be, one or two days. A cul- 
ture-tube is prepared, sent to the municipal laboratory, examined, 
and the result sent back to the practitioner, who then goes to see the 
patient. It is very fortunate if not more than one day is lost in this 
way, and the loss of those hours may well mean the loss of life, for 
the time has elapsed during which the antitoxin would best act. 
There is no reason at present for believing that the antitoxin used in 
moderate quantity does harm when the child has not diphtheria. 
When, therefore, any case presents the clinical aspect of diphtheria 



ALTERATIVES 



10!) 



the antitoxin should be used at once. For educational purposes, and 
for rendering definite our knowledge, the municipal laboratories 
are very useful; for purposes of treatment the less attention paid to 
them probably the better for the patients. 

The greatest danger after that of not using diphtheria antitoxin 
early enough is that it be not given freely enough. The ordinary 
dose of diphtheria antitoxin for an adult is from two thousand to 
five thousand units, according to the severity of the case. In very 
virulent cases, however, it may be advisable to exceed this dose, 
since frequently when the ordinary quantity fails a dose of ten thous- 
and to twelve thousand units proves efficacious. Since the injections 
are practically harmless, it seems better to err on the side of too large 
than too small dosage, although Musser has recommended the use of 
comparatively small doses of five hundred to one thousand units 
repeated at frequent intervals every six hours. It is affirmed that 
the milder method is less likely to be followed by disagreeable anti- 
toxin symptoms; but as these disagreeable symptoms are of little 
importance, the superior promptness and certainty and the avoidance 
of frequent disturbance of the patient, which attend the more heroic 
method, seem to us to make it preferable. 

The dose of antitoxin for children should be proportionately 
much larger than in adults, and the American Pediatric Society 
recommends that in children over two years of age, in cases of mod- 
erate severity, from fifteen hundred to two thousand units should 
form the initial dose; in children under two years, quantities up to 
one thousand units may be given. 

Antidiphtheric serum is also serviceable as a prophylactic in well 
persons who have been exposed to the infection. In this case the 
dose should be from 500 to 1000 units. 

The use of antitoxin in any case of diphtheria should not interfere 
with the usual local and general treatment. 

The antitoxin solution should be injected deeply into the buttocks 
or back with every possible antiseptic precaution. 

In most cases the injection of the antitoxin is followed in a very 
few hours by a fall of temperature and a decrease of the local diph- 
theritic symptoms. Occasionally, but not usually, this ameliora- 
tion is preceded by a temporary rise of temperature. Sometimes 
the disagreeable symptoms produced by the injection appear in a 
few hours; perhaps more commonly they are not developed until 
from six to nine days; and it is even affirmed that they may be 
delayed to nine weeks, and that they have led to the mistaken diag- 
nosis of scarlet fever or other exanthema. The characteristic symp- 
toms are rise of temperature, w 7 ith eruption upon the skin, and rarely 
swelling and pain in the joints. The skin eruption may be purely 
erythematous, is often scarlatinoid, and perhaps as frequently 
rubeoloid, and sometimes it takes the form of a severe urticaria. 

The unpleasant effects which follow the injection of diphtheria 
antitoxin seem to be due rather to the introduction of the foreign 



410 GENERAL REMEDIES 

serum into the blood, than to the antitoxin itself. The attempt has 
been made to prepare an antitoxin which shall be free from these 
poisonous albuminous bodies. The methods employed are based 
upon the fact that the antitoxin is in the nature of a globulin and is 
precipitated from the blood serum by a saturated solution of ammo- 
nium sulphate, while most of the album' nous bodies in the blood 
serum are not. (See Park and Throne.) 

Tetanus. — Despite the vigorous claims of various scientific author- 
ities concerning the value of tetanus antitoxin, the results with this 
method of treatment have not been very brilliant. Goodrich, in a 
collection of two hundred and twenty-six reported cases, found that 
sixty-four per cent, of those treated by other methods recovered, and 
only sixty-three per cent, of those treated by antitoxin. The pub- 
lished mortality of other authors who have employed tetanus 
antitoxin varies from thirty-five to sixty per cent. 

In the laboratory, tetanus in the lower animals can be cured with 
almost absolute certainty by the proper use of antitoxin. The causes 
of the discrepancy between laboratory and practical results have 
been pointed out by Tsuzuki. This author found that tetanus anti- 
toxin was capable of saving mice only when the dose of the toxin 
was not more than two or three times the minimum fatal dose, and 
when the antitoxin was injected within six hours after the adminis- 
tration of the toxin. He further found that the antitoxin had much 
more effect if injected in the neighborhood of the inoculation with 
the toxin than when administered subcutaneously in another part 
of the body. 

It is very evident from these results that, in cases of human 
tetanus, where the virulence of the infection is unknown and where 
there is usually a considerable amount of toxin in the system before 
the outbreak of the symptoms, tetanus antitoxin cannot be expected 
to rank as an infallible cure for this disease. Nevertheless, especially 
in those cases which are seen early, the immediate use of antitoxin, 
since it need not interfere with other methods of treatment, appears 
to be advisable. There is also much evidence of its value as a 
prophylactic. 

The United States Marine Hospital Service has established a 
unit for antitetanic serum which is compulsory for American makers 
of serum. The dose is from 2000 to 5000 of these units. 

Streptococcus Infections. — The streptococcus antitoxin has been 
recommended in the treatment of erysipelas, puerperal septicemia, and 
similar conditions. The reports of the results, however, do not seem 
to be very encouraging. In three hundred and fifty cases collected 
by the American Gynecological Society, the mortality in puerperal 
sepsis treated with streptococcus antitoxin was thirty-three per cent., 
which is no less than the ordinary mortality rate in these cases. It 
is evident that a streptococcus antitoxin can prove of no value in 
staphylococcus infections. Streptococcus antitoxin has also been 
used in the treatment of secondary infections with the streptococcus 



ALTERATIVES 411 

occurring in diphtheria and scarlet fever. There is no generally recog- 
nized unit of streptococcus antitoxin, and therefore cannot be any 
definite dosage; so that the practitioner can only follow the directions 
given with the antitoxin serum by the manufacturing firm. 

Cholera. — Lazarus discovered that the blood-serum of human 
beings who have recovered from an attack of Asiatic cholera possesses 
properties which render it capable of protecting animals from fatal 
doses of the spirillum of Asiatic cholera. He regarded this substance 
as being of the nature of an antitoxin, and the protective action of the 
human serum as similar to the antitoxin of diphtheria, tetanus, etc. 
The studies of R. Pfeiffer, however, have shown that the principle 
contained within the blood-serum is not of the nature of an antitoxin, 
but is bactericidal; it acts by causing rapid disintegration of the 
introduced cholera organism, and thus prevents the rapid multipli- 
cation that brings about the death of the exposed animal. A few 
minutes after the simultaneous introduction of the cholera vibrio 
and of the blood-serum into the peritoneal cavity of small animals, 
such as the guinea-pigs, the micro-organisms begin to disintegrate, 
and very soon they are completely destroyed. 

Pfeiffer also showed that dead cholera organisms are still toxic and 
capable of acting similarly to the living germs. Haffkine has origi- 
nated a method for the immunization of human beings against cholera; 
he cultivates the germ in bouillon, and after a certain growth has been 
obtained, heats sufficiently to kill the germ without completely 
destroying the cholera poison which adheres to its body, and which 
is a very sensitive substance. Injections of such cultures in human 
beings are followed by a local reaction and febrile movements and the 
appearance of a protective substance in the blood-serum in man 
similar to that present after an attack of the disease. Two injections 
are commonly made at the interval of about a week, after which the 
protection of the individual is believed to be complete. This method 
has been applied on a large scale in India, and apparently with a 
measure of success. 

Hay-Fever. — Dunbar's Hay Fever Antitoxin is at present obtained 
by inocculating healthy horses with a toxin obtained from the pollen 
of certain flowering grasses and plants. Dunbar in 1903 isolated from 
the pollen an active toxin the exact nature of which he could not 
determine further than saying it was a toxalbumin. Hay-fever 
patients showed a marked reaction to this toxin, at any time of the 
year, if it was brought in contact with the mucous membrane or 
injected subcutaneously and these attacks were instantly relieved by 
the application of the antitoxin. , 

When Dunbar's antitoxin was first used in America, the reported 
results by Mayer, McCoy and others were so favorable that the use 
of the treatment rapidly spread. In the year 1904, the results 
obtained were not so favorable and the use of the antitoxin rapidly 
sank in popularity. This difference in results is probably dependant 
on the difference between European hay-fever which occurs in the 



412 GENERAL REMEDIES 

early summer and the American type which occurs in the late Summer 
or early Fall. The first cases in this country were treated by an anti- 
toxin especially prepared by Dunbar and his assistants from rag- 
weed pollen and sent to a few well-known specialists. In the summer 
of 1904 the product obtained was that produced by Schimmell & 
Co., from flowering grasses and was used promiscuously without 
attention to detail. From the results of 1903 and 1904, it seems that 
in America, the antitoxin to be of any value must be prepared from 
the pollen of goldenrod, ragweed or one of the toxic plants which 
bloom late in the summer. In exceptional cases of mild hay-fever, 
frequently called rose cold, the antitoxin prepared from the grasses 
is more efficient. The results of the summer of 1905 confirm this 
assumption and since the antitoxin prepared by Schimmell & Com- 
pany was put on the market and more attention given to the 
treatment in details, the results were very favorable. 

The present status of the antitoxin treatment of hay-fever is that 
in the majority of cases of true hay-fever in which the attack begins 
about the second week in August, the careful use of the antitoxin 
will give more or less benefit. To obtain the greatest relief the treat- 
ment should begin 4 or 5 days before the expected attack and keep 
up regularly throughout the whole hay-fever season. References to 
the literature may be found in the article of H. W. Loeb. 

Bubonic Plague. — Pest. — The discovery by Yersin, in 1894, of the 
bacillus of the bubonic plague has caused protective measures to be 
employed in combating that disease. Several methods are now in 
use; that of Yersin consists in the immunization of horses or other 
large animals to injections of the plague bacillus, and the use of the 
blood-serum obtained from these animals in a manner similar to the 
employment of the antitoxin of diphtheria. 

Haffkine's method, which has been used on a larger scale, and 
apparently with less doubtful results than that of Yersin, is in prin- 
ciple similar to the protective inoculation for cholera. Bouillon cultures 
of the plague bacillus (the organisms being obtained directly from 
human cases of the plague) are incubated for about two weeks. The 
bouillon is finally heated to 60° C, for about twenty minutes, in order 
to kill the bacillus, after which half of one per cent, of phenol is added 
in order to preserve the serum from accidental contamination by 
micro-organisms. The injections are made into the soft tissues of 
the thigh, the entire culture being used. Two injections are usually 
employed, at intervals of six days. The symptoms are elevation of 
temperature and swelling about the point of inoculation, most marked 
after the first injection. The second inoculation is believed to give 
protection. The statistics gathered from India, where the plague 
has prevailed, are highly encouraging as to the value of this pro- 
cedure. The serum is of no use in the treatment of developed cases 
of the plague. 

Another method of protection which is being employed is that of 
Lustig, who produces from the dead plague bacillus, by treatment 



ALTK RAT INKS 413 

with acids and then alkalies, a nuclco-protcid, whose inoculation 
into animals and human beings gives active immunity to the plague 
organism. The blood-serum from animals so immunized may be used 
in the treatment of the developed plague; or, injected into healthy 
human beings, affords a passive immunity which, however, endures 
only a few weeks. It is, therefore, capable of use in protecting for 
a short time a community exposed to the plague, although less reli- 
able than Haffkine's serum. Its advantage is that it affords immediate 
protection, whereas the other means employed require a number of 
doses before the protective action appears. 

The blood-serum of human beings and animals who have with- 
stood injections of the plague bacillus possesses agglutinating prop- 
erties for the plague organisms; this agglutination, however, does not 
appear early in the infection, but is a phenomenon of convalescence. 
Its usefulness, therefore, in the diagnosis of plague is doubtful. 

Snake- poisoning. — Ccwall appears to have been the first to demon- 
strate the possibility of producing immunization against the venom 
of serpents, having proved as long ago as 1887 that it was possible 
by a series of inoculations of increasing intensity temporarily to 
immunize pigeons against the rattlesnake-poison. 

The serum of the blood of the artificially immunized animal has 
been found to be of remedial value in snake-poisoning, and has been 
put upon the market commercially. Its use as a prophylactic is 
justifiable only in certain conditions when there is about to be an 
extraordinary exposure to a possible snake-bite, since the immunity 
it confers lasts only for a short time. The value of the serum as a 
curative agent has, however, been proven not only in the laboratory 
but also in a number of recorded cases of snake-bite; so that it should 
be carried by those whose duties or desires lead them into tropical 
countries where poisonous serpents abound. 

Antitoxin for snake-venom, suggested almost simultaneously by Pliisalix and 
Bertrand, and Calmette, was first practically prepared by Calmette. As was origi- 
nally shown bj Mitchell and Reichert, snake-venom contains two toxic substances — 
a local and a constitutional poison. The serum of Calmette is prepared from cobra- 
venom, which contains comparatively little of the local irritant, and, according to 
McFarland, immunizes only against the generally acting element of snake-venoms. 
Poisons of the American snakes, such as the rattlesnake, the moccasin, etc., are 
mostly liighly irritating venenes. In an effort to produce an antitoxin which would 
be efficacious against these serpents, McFarland was unsuccessful in producing an 
immunity in the horse to the local irritant action of the poison, although he obtained 
a serum which overcame the constitutional effect of these venoms. Although 
Calmette claims that his antitoxin is efficacious not only against various serpent- 
poisons, but against scorpion-bites, McFarland lias shown that although it destroys 
the nerve-depressant poison it does not overcome the effects of a great local irrita- 
tion which is caused by such venoms as rattlesnake-poisoning, and is not a sure 
life-saving remedy. More recently Noguchi lias succeeded in obtaining a rattle- 
snake antivenin. Fraser asserts, however, that the dose of antivenin required to 
afford an efficient degree of immunity is so large as to make it impracticable in 
human poisoning. He claims that 350 C.c. are necessary to cure a man of one 
hundred and seventy pounds weight; the ordinary quantity recommended is 15 
to 20 C.c. 



414 GENERAL REMEDIES 

As the result of experiments by various observers, it has been 
established that venomous serpents are poisoned by snake-venom 
only with the greatest difficulty; that the ordinary non-poisonous 
snakes share this immunity to a distinctly less degree; and that 
certain of the higher animals, notably the mongoose, are distinctly 
resistant to the poison. It is probable that the immunity in the 
higher animals is an inherited, "acquired character," due to the 
repeated survival of generations of bitten animals, the immunity of 
the individual being partially transmitted to the offspring. 

According to the reports of missionaries, the various compounds 
prepared by the "witches" in Africa for the cure of snake-bite have 
the liver of the serpent in their combination; and T. R. Fraser, of 
Edinburgh, has experimentally proved that the bile of poisonous 
serpents is a very active antidote to the poison, neutralizing the 
venom when mixed with it in equal quantities. Even the bile of 
ordinary snakes has a feeble antidotal power. When after a bite it 
is possible to kill the snake, all of its bile should be injected into the 
immediate neighborhood of the wound. 

OPSONINS. 

In 1903 Sir Almoth Wright announced the discovery that for 
phagocytosis to take place there was necessary certain constituents 
in the blood serum which he assumed acted upon the bacteria to 
prepare them for leucocytic destruction. These bodies, the nature 
of which is not yet definitely proven, were by him called opsonins. 
Wright and his followers have further shown that in certain condi- 
tions the amount of opsonin in the blood may become markedly re- 
duced so that phagocytosis takes place much less actively and the 
body becomes correspondingly more susceptible to bacterial invasion. 
The figures indicating the power of the blood serum to render bacteria 
destructible by leucocytes in comparison to the activity of normal 
serum, is known as the opsonic index. The opsonic index may fre- 
quently be greatly increased by various appropriate measures, one 
of the most potent of which is the presence of bacterial toxins 
in the blood. 

From these observations there has arisen in the last few years a 
new method of treating infectious diseases by injection of emulsions 
of dead bacteria. It is perhaps hardly accurate to speak of this method 
as new as it has been emplo3 r ed for many years in the treatment of 
tuberculosis and is very similar to that employed by Haffkin as a 
protection against cholera. (See page 411.) 

As pointed out by Ross there are three classes of cases of bacterial 
infections presenting low opsonic indices. The first of these com- 
prises local infections in which the bacterial products have not entered 
the general circulation and there is, therefore, lacking the reactive 
stimulation of the general system. The second group comprises 
cases in which the bacterial invasion of the general system is so great 



ALTERATIVES 415 

as to apparently overwhelm the opsonogenic powers of the system. 
The third class of cases includes those of such low vitality that they 
are not able to react to the stimulant influence of the toxins. Mani- 
festly it is only in the first group of cases that the treatment of 
bacterial inoculations can be expected to give beneficial results. 

This group of cases includes first, a large number of bacterial 
skin diseases, as, funinculosis, acne, sycosis, and the like. Secondly, 
localized infections by pyogenic organisms, as carbuncles, boils and 
walled abscesses. Ami finally, early cases of pulmonary tuberculosis 
in which the disease assumes a local infection of the lungs rather than 
a systemic morbid process. The treatment of tuberculosis by means 
of the toxins of the tubercle bacilli was introduced by Koch many 
years ago. His method was later modified so that instead of the toxin 
the bacteria themselves previously devitalized by heating were 
injected. The method has been commended by various clinical 
authorities, notably Von Ruck, but has become especially popular 
since the explanation of the modus operandi was offered by Wright's 
opsonic theory. While the results from the injection of tuberculin 
have not been so brilliant as opsonic therapy in some other infections 
yet the trend of evidence to-day is that it possesses distinct value in 
certain cases, especially in the early stages.* 

Apparently the opsonins are specific, that is, for each different 
variety of bacteria there is necessary for phagocytosis to occur, the 
presence of a definite element in the blood so that the opsonic index 
may be very high for one organism and low for another. While it is 
impossible in a work of this character to go into the detailed descrip- 
tion of the opsonic therapeutic method, we will briefly mention the 
general principles involved. It is first necessary to determine the 
opsonic index of the patient for the infection from which he is suffer- 
ing. For this purpose the micro-organism which is the cause of the 
trouble is cultivated on an ordinary media and an emulsion of definite 
strength is made. The patient's serum is obtained from a blood clot 
and added to a mixture of washed leucocytes and bacteria, and the 
number of bacteria found within the leucocytes counted. A similar 
operation is performed using serum of a healthy individual with all 
other conditions precisely similar, and the figures compared. A 
culture is then made of the bacteria and heated to a temperature 
of 60° to 70° C. (140° to 150° F.) to kill the bacteria, and doses 
of several million dead bacteria injected subcutaneously. It is gen- 
erally preferable to employ cultures made from bacteria obtained 
directly from the patient, although if the species of bacteria is 
definitely known the same variety obtained from other sources may 
be employed. 

* Tuberculin is also largely used as a diagnostic measure by the veterinarian, and occasionally 
in human medicine. When tuberculin — that is, tubercular toxin — is injected into the blood in 
certain small quantity, it produces no febrile reaction in the normal individual because there is 
not enough of it present in the system. If, however, the injected toxin be added to a toxin which 
has been previously produced in the body, and which is already in the blood, the aggregate 
amount will be capable of producing a hectic fever, which will demonstrate the existence of a 
toxin-producing focus in the body, — i.e., of tuberculosis. 



416 



GENERAL REMEDIES 



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.V. A. P. A., xlvi. 302; 

Teissier, Le Mouvemcnt 

Med., Sept., 1875. 
.7.. Bi., xvi., 198. 



COLCHICUM. 

Albers D. Kl., 1S56, xxxvi. 

BIRD Urinary Deposits, Phila., 

1859, 354. 
Dixon Manual of Pharmacology, 

1900, p. 96. 

Ferrer U. M. M., i. 

Garrod M. C. Tr„ 1858, xli. 348. 

Hammond Proc. Aead. Nat. Sci., Phila. 

Dec., 1858. 

Kionka Z. E. P. T., ii. p. 9. 

Kkaiimer Journ. f. Pharmakol., ii. 561. 

Lewins Edinburg Med. Surg. Journ., 

1841, lvi. 200. 
Maclagan Edinburg Journ. Med. Sci., 

3 s., xiv. 24. 

Paschkis S. Jb., cci. 232. 

Patton B. M. J., 1886, i. 

Rossbach Pharmak. Untersuch., ii. 

Schulz Wien. Med. Presse, 1897, 

xxxviii. 31. 

Taylor Med. Jurisprud., 2d ed., i. 

Wood U. S. Dispensatory, 13th ed., 

1504. 

Surer M. A., 1902. 

Vox Hebra M. P. D., 1893. 

SARSAPARILLA. 



BOECEER. . . . 


. . . . Journ. f. Pharmak., ii. 23. 




JAMBUL. 


Bl.NZ 

Christy 


. . . . Verhandl. Cong. f. imiere 
Med., Weisbaden, 1886. 

P. J. and Tr. 1888. 

Th. M., 1893. 




GELATIN. 



Bertima and Besdetnoff. .Merck's Report, 

1900, 105. 
Camus and Gley .C. R. S. B., 1898, v. 1041. 
Dastre and Floresco. .C. R. S. B., 1896, ii. 

668; iii. 243. 
Freudweiler .... Cb. I. M., July 7, 1900. 

Hahn M. M. W., 1900, 1459. 

Kehr M. M. W., 1900, 181. 

Lancere.vux and Paulesco..B. A. M., 1898, 

578. 
Lancereatjx B. A. M„ 1898, 353; Ther. 

Geg. 1900, ii. 397. 
Lemoine Th. M., 1900, 284. 



418 



GENERAL REMEDIES 



REFERENCES (Continued). 



Manicotide and Christodulo. . K. T. W.,1899, 



Moll 

Rocchi. . . 

SCHWABE. . 

Wood, Jr. 
Zibell 



vi. 696. 
. .W. K. R., 1904, xviii. 580. 
. .M. M. W., 1900, 1613. 
. .Th. M., 1900, xiv. 312. 
. .Am. Med., 1902, iii. 729. 
. .M. M. W., 1901, 1640. 



THYROID BODY. 

Ballet and Enriquez. .M<5d. Mod., 1895, vi. 

Baumann Z. P. C, 1895, xxi. 

Baumann and Goldmann. . M. M. W., 1896. 
Bell Phys. and Surg., 1898, xx. 

309. 

Bergmann S. Jb., 1897, ccliii. 18. 

Bettmann B. K. W., 1897, xxxiv. 

David Zeitsch. f. Heilk., 1896, 

xvii. 439. 
Diaballa and Illyes. .A. E. P. P., 1897, 

xxxix. 273. 
Dobrowsky Ann. d. Kinderheilk., 1896, 

xxi. 
Fraenkel Aertzl. Central. Anzeiger, 

1895. 
Gluzinski and Limberger. .Centralbl. f. in- 

nere Med.. 1897, xviii. 4. 

Gottlieb D. M. W., 1896 xxii. 

Gould B. M. J., 1898, ii. 

Haskovec W. M. B., 1895, xviii.; A. I. 

P. T., 1901, viii. 167. 

Hertoghe B. A. K. B., 1896. 

Hildebrandt . . . .B. K. W., 1896, xxxiii. 

Hutchinson B. M. J., 1896, i. 

Irsai, Vas and Gara. .D. M. W., 1896, xxii. 

James B. M. J., Aug. 4. 1894. 

Lepine Lyon M., 1896, Ixxxii. 

Levy D. M. W., 1896. 

Magnus-Levy. . . .S. Jb. ccliii. 19; D. M. W., 

1896, xxii. 

Mayer D. M. W., 1896, xxii. 

Mosely M. News. 1898, lxxii. 353. 

Murray Annals of Surgery, 1900, 

xxxi. 696. 
Oliver and Schaefer. .J. P., 1895. 

Ott Med. Bull., 1898, xx. 89. 

Perry N. Y. M. R., 1896. 

Poyes B. K. W„ 1900, xxxvii. 300. 

Richter Centralbl. f. innere Med., 

1896, 65. 

Roos Z. P. C, 1896, xxi. 

Roos M. M. W., 1896, xliii. 

Schoendorff A. G. P., 1896, lxiii. 423; 

A. G. P., 1897, lxvii. 395. 
Scholz Centralbl. f . innere Med., 

1895, 104. 
Vamossy and Vas. .M. M. W., 1897, xliv. 
Wormser A. G. P., lxvii. 505. 



PITUITARY BODY. 

Cyon A. G. P., 1898, lxxiii. 

Howell J. Ex. M., 1898. 

Mairet and Bosc.A. de P., 1896, 100. 
Oliver and Schaefer. .J. P., 1895, xviii. 

Schiff Z. K. M., 1897, xxxii., Suppl. 

284. 



Clark. . . . 



SPLEEN. 

.Ed. M. J., 1898, iii. 152. 



THYMUS GLAND. 

Mackenzie A. J. M. S., 1897, cxiii. 

ANTITOXINS. 

Behring D. M. W., 1900, xxvi. 29. 

Goodrich Annals of Surgery, Dec. 1897 

Haffkine B. M. J., 1893, i. 278; 1895, 

ii. 1541. 
Loeb Ann. Otol. Rhin. Laryng., 

June, 1905. 

Musser U. M. M., March, 1G00. 

Park and Throne. .Trans. Ass. Amer. Phys., 

1906, xxi., 259. 
Tsuzuki A. I. P. T., 1901, viii. 19. 

SNAKE POISON. 

Calmette C.R.S.B., 1894, 10 s., i. Ill, 

Ann. de l'lnst. Pasteur, 

1895, ix. 225. 

Fraser B. M. J., 1896, i. 957. 

McFasland J. A. M. A., Dec. 14, 1901. 

Mitchf.lt, and Reichert . . Publications of the 

Smithsonian Institute 

1886. 

Noguchi U. P. M. B., 1904, xvii. 154. 

Phisalix and Bertrand . . C. R. A. S., 1894 

cxviii. 356; 1895, cxxi.. 

754. 

LECITHIN. 

Claude and Zaky. .R. T., 1901, lxviii. 
Danilewsky C. R. S. B., 1897, iv.; 

C. R. A. S., 1896, cxxiii.; 

A. G. P., 1895, lxi. 
Gilbert and Fournier. .C. R. S. B., 1901, liii. 
Lancereaux and Paulesco. .B. A. M., 1901. 

xlv. 

Serono A. I. B., 1897, xxvii. 

Wood Jr U. P. M. B., 1902. 



OPSONINS. 

J. A. M. A., xlix. 1243. 

Journal of Tuberculosis 1903, 

v. 165. 
B. M. J., 1903 i. 1069. 



Ross 

Von Ruck. 



Wright. 



FAMILY IV.— ANTIPERIODICS. 



CINCHONA. 



The trees comprising the genus Cinchona, of which there are many 
species recognized by botanists, are handsome evergreens indigenous 
to South America, especially along the slopes of the Andes at an 
altitude of from five to ten thousand feet above the level of the sea. 
The U. S. Pharmacopoeia recognizes the Cinchona ledgeriana, calisaya 
officinalis and — under the name of cinchona rubra — the Cinchona 
succirubra, as well as various hybrids of these species. 

It is uncertain, but improbable that the South American natives 
were acquainted with the medical properties of cinchona. The ear- 
liest record of its use appears to be in 1630, when Canizares who was 
then governor of Loxa, one of the divisions of Peru, was cured of 
ague by its use. In 1638, the Countess of Cinchon, wife of the viceroy 
of Peru was cured by the bark and sent a quantity of the remedy to 
Europe where it was employed under the various names of "countess 
bark," "Peruvian bark," etc. In the early part of the last century 
it became evident that owing to the reckless methods of collecting 
the bark that the natural source would soon be exhausted, and after 
various efforts to establish artificial plantations, the Dutch finally 
succeeded, in 1853, in starting a successful cinchona grove in the 
island of Java. Since then the tree has also been successfully culti- 
vated in India and Ceylon. Of the nearly eighteen million pounds 
of cinchona bark produced annually, over fifteen million pounds come 
from the island of Java, and about seven hundred thousand pounds 
from South America. 

The official portion of the tree is the bark, which occurs in quills 
or curved bits of various size, externally of a grayish color, interior 
brown, and with a very bitter and somewhat astringent taste. 

Although the cinchona bark contains a large number of alkaloids, 
only four are present in sufficient proportion to be of any practical 
importance. They are, — quinine, cinchonine, cinchonidine and 
quinidine. Of these the first three are official. The bark should 
contain not less than five per cent, of total alkaloids. 

Official Preparations : 

Fluidextractum Cinchona 15 to 30 minims (1-2 C.c). 

Tinctura Cinchonse (20 per cent.) 1 to 2 fluidrachms (4-8 C.c). 

Tinctura Cinchonae Composita (Huxham's 

Tincture) 10 per cent 1 to 2 fluidrachms (4-8 C.c). 

Quinina 2 to 5 grains (0.13-0.3 Gm.). 

Quinimc Sulphas 2 to 10 grains (0.13-0.6 Gm.). 

419 



420 GENERAL REMEDIES 

Official Preparations {Continued). 

Quininaj Bisulphas 2 to 10 grains (0.13-0.6 Gm.). 

Quininae Hydrobromidum 2 to 10 grains (0.13-0.6 Gm.). 

Quininae Hydrochloridum 2 to 10 grains (0.13-0.6 Gm.). 

Quininae Salicylas 2 to 10 grains (0.13-0.6 Gm.). 

Cinehonidinae Sulphas 3 to 15 grains (0.2-1.0 Gm.). 

Cinchoninae Sulphas 3 to 15 grains (0.2-1.0 Gm.). 

Quinine was first distinctly separated from the other ingredients 
of the bark by Pelletier and Caventou in 1820. 

The neutral, official quinine sulphate occurs in light silky crystals, 
soluble in seven hundred and twenty parts of cold or in thirty of 
boiling water, but very freely so in acidulated solutions. Therefore, 
when it is administered either by the subcellular tissue or by the 
rectum the alkaloid should be given in the form of the bisulphate 
and in distinctly acidulated water. 

Physiological Action. — Local Action. — Quinine is distinctly 
irritant to the mucous membranes, but has little or no influence upon 
the sound skin. It was stated as long ago as 1765 by Pringle, that 
cinchona bark itself is distinctly antiseptic and has been confirmed 
by Hallier, Binz and others. More recent researches have demon- 
strated that quinine is actively germicidal, and that in the proportion 
or one part to three hundred it will preserve for a long time flesh, 
meal, milk, butter, urine, albumin, etc., and will check very markedly 
the alcoholic fermentation in honey or in syrup. 

According to the experiments of Binz, the larger infusoria, such as Paramecia 
and Colpoda, are killed by a solution of quinine of the strength of 1 in 800 immedi- 
ately, of 1 in 1000 after some minutes, of 1 in 20,000 after some hours. Upon the 
ordinary mould Penicillium, upon Vibrios and Bacteria, as well as upon the 
higher infusoria, quinine acts with a similar fatality. In the case of the Vibrios 
and Bacteria a decidedly stronger solution than the one mentioned is required to 
quiet movement. Bochefontaine found that a solution of one per cent, was needed 
for a vigorous rapid action, and that some active granules could even be found in 
it after three days. 

The fact that fungi will appear after a time in an ordinary solu- 
tion of quinine sulphate demonstrates that at least upon some of the 
lower organisms it has but comparatively little influence, although 
on others it acts with much power. 

Absorption and Elimination. — Owing to its insolubility in simple 
water or alkaline solutions, quinine can enter the body with rapidity 
only under circumstances in which it is exposed to the solvent power 
of acids. 

Taken into the stomach, the quinine salt is dissolved by the acid 
gastric juice; but if it be not absorbed at once, passing into the intes- 
tines it is liable to be precipitated by the alkaline juices and the bile 
salts. 



^NTIPERIODICS l-M 

Quinine is eliminated chiefly through the kidneys, escaping in 
large part unchanged, bui probably in pari undergoing alteration.* 

Thai a considerable portion of Ingested quinine can be recovered from the 
feces has been pi-oven by Kerner and other chemists. It is probable, however, thai 
some of this fecal quinine has been absorbed and subsequently cast out by the liver 

as a. very insoluble biliary salt, since Albertoni and t'iotto found that when they 
injected quinine into the jugular vein it failed lo appear in the bile, although when 
given by the mouth it was freely eliminated with that secretion. 

According to Briquet, quinine may generally be found in the urine half an hour 
alter the administration of a large dose. Its removal, according to the researches 
of Bins, goes on slowly, for it is stated that in six experiments only a little more 
than two-thirds of the ingested quantity was excreted in the first, forty-eight hours. 
Further, De Renzi, Yvon, and Diet! have found it in the urine six or seven days 
after the ingestion of the last dose. It is probable that some of the quinine is elimi- 
nated through other channels than the kidneys, since Binz had found it in the saliva 
of a poisoned dog, and Landerer states that he has detected it in the urine, sweat, 
(cars, milk of nursing women, and in the serum of dropsical effusions, while Albertoni 
and De Renzi found it abundant in the bile when it had been taken by the mouth, 
but not when it had been given hypodermic-ally. Merkel discovered that in the 
dog from eighty-six to eighty-eight per cent, of the quinine escaped unchanged 
from the kidneys, the remainder being converted into new substances. F. K. Kleine 
determined that 29 per cent, escaped through the urine in twenty four hours, the 
elimination being at its height in about six hours after the taking of the drug. 

As the blood is alkaline, a priori, it would be expected that the 
quinine salt would be precipitated in the blood; that this does not 
occur is, according to the researches of Kerner, due to the solvent 
power of the carbonic acid in normal blood. 

The authority mentioned found that- one thousand parts of blood which was 
ilefibrinated and deprived of its gases at a temperature of 36° C. dissolved in an 
hour only 0.398 part of pure quinine. Water saturated with carbonic acid gas 
dissolves the quinine sulphate pretty freely; and Kerner also experimentally deter- 
mined that when a neutral solution of a salt of quinine is added to a very dilute 
solution of sodium carbonate no precipitate occurs. It would appear, then, that 
the quinine is held in solution in the blood by reason of the loosely combined 
carbonic acid gas in that fluid. 

The question as to the rate and completeness of the elimination 
of quinine is one of great practical importance. It is evident that it 
is both absorbed and eliminated more rapidly when it is given in 
solution or in the form of the acid salt than when taken in pill or 
capsule. Under favorable circumstances, with the dose not too large, 
it is probable that absorption is practically complete within two 
hours after the taking of the quinine into the stomach, so that the 
maximum effect of the single dose is probably reached in from one 
to two hours. Thau determined that from a third to somewhat 

* G. Kerner (Pfiiiger's Archiv fur Physiolcgie, 1870) asserts that the quinine as excreted is in 
an amorphous, uncrystallizable form. He also has discovered in the urine of persons taking quinine 
a peculiar substance, sometimes amorphous, sometimes in acicular prismatic crystals, free from 
bitter taste, possessing the quinine inflorescence, which he believes to be a derivative formed in 
the body from the ingested alkaloid. He has not been able to get this substance in such quantity 
as to analyze it or further examine it, but has produced a principle (dihydroxyl-quinine) which he 
believes to be identical with it by acting on quinine with the potassium permanganate. An elaborate 
series of experiments have shown that the dihydroxyl-quinine is physiologically inert. This dihy- 
droxyl-quinine must be produced in small amount, if at all, as there is abundant evidence that 
quinine is largely excreted as quinine (see Pharm. Journ. and Trans., ix. 125). 



422 GENERAL REMEDIES 

less than half of the ingested quinine escapes from the body in the 
first six hours, and that in the first twelve hours about three-fourths 
are excreted. Welitschkowski found an elimination of sixty-five per 
cent, the first day and twenty-five per cent, the second day. Prior 
gives the second day as the usual final limit of elimination. We think 
it more than probable that after a few doses the alkaloid is practically 
eliminated in forty-eight hours, but that when it has been given con- 
tinuously, or when kidney disease or great feebleness of circulation 
exists, the system may contain a notable amount of the quinine for 
a longer period. The researches of Welitschkowski are in accord with 
those of Jiirgensen and Thau in showing that in cardiac and renal 
disease and in low fevers elimination proceeds very slowly, more of 
the alkaloid being thrown off in the second than in the first six hours 
after its ingestion. 

Physiological Action. — Nervous System. — In the lower animals 
large doses of quinine frequently cause violent epileptiform convul- 
sions. Given to dogs in sufficient quantity, it produces restlessness, 
followed by muscular tremblings, which have been compared to those 
of paralysis agitans, loss of power deepening into more or less com- 
plete paralysis, great dyspnoea, and cerebral symptoms, such as 
anesthesia, blindness, stupor, or violent delirium, dilated pupils, 
coma, and convulsions. Death has been shown by Heubach to be 
produced, at least in the lower animals, by a failure of the respiration. 
The cause of the convulsions in the lower animals is unknown. In 
the frog quinine lessens reflex activity probably by stimulating the 
spinal inhibitory mechanism (Setschenow's centre). This action 
may explain some of the therapeutic virtues of the drug. 

The experiments of Albertoni would indicate that quinine is capable of con- 
vulsing both the pigeon and dog after destruction of the cerebrum. Although in 
the frog it causes some temporary increase of reflex activity its stimulant action 
upon the cord is not sufficient to account for its convulsive action. In this connec- 
tion the fact noted by Brown-Sequard, and confirmed by Albertoni, that the cin- 
chona alkaloids increase the frequency of the seizures in epileptics, becomes of 
great interest. When given to the frog in large doses quinine lessens the reflex action 
apparently by the effect upon the spinal inhibitory mechanism, although in toxic- 
quantities it also has a direct depressant action upon the motor cord. Jakoubowich 
has noted the epileptiform convulsions in dogs from quinine and it has been pro- 
duced by cinchonidine in various animals. Chirone and Curci found that in the 
pigeon this action of cinchonidine is prevented by ablation of the cerebral hemi- 
spheres, but Albertoni objects with much force that these observers gave the pigeon 
the alkaloid too soon after the ablation, while it was still profoundly affected by the 
shock and hemorrhage of the operation. Albertoni found that, if the pigeon is 
allowed to recover, the cinchonidine is capable of causing convulsions; also that 
in dogs with the motor zone of the cerebral cortex destroyed, the alkaloid causes 
epileptiform attacks, and that therapeutic doses do not increase the excitability of 
the cerebral cortex in the dog. 

Louis Dupuis found that reflex action may be normal in poisoned dogs and 
rabbits, although there is complete loss of sensibility: if this be correct, the toxic 
dose of quinine must paralyze the perceptive centres in the cerebrum. 

According to the experiments of Briquet, a solution of quinine sulphate injected 
into the carotid will in some cases produce meningitis. In doing this, it is evident 



ANTIPERIODICS 423 

(hat the salt acts as an irritant to the membranes of (lie brain rather than as a 
nervous stimulant: indeed, experimental evidence proving that quinine is a 
oerebraJ stimulant seems to us to be wanting. 

Sohlockow was the hrst to notice a stage of increased reflex activity produced 
in the frog by quinine; its existence was subsequently denied by A. Eulenburg, 
but has been reallirmed by 11. lleubaoh and by David Cerna, who agree in finding 
thai it occurs only alter very minute doses. In his investigations made in the 
laboratory of the University of Pennsylvania, Cerna found that this stage of excite- 
ment is probably caused by a stimulant influence upon the peripheral sensory nerves, 
as it did not occur when the abdominal aorta was tied previous to the exhibition of 
the alkaloid. Two facts, first pointed out by T. A. Chaperon, have been so abund- 
antly substantiated that we must accept them as established. They are, that in 
small doses quinine causes in the frog a lessening of the reflex activity, which is 
removed by section of the medulla, and in large doses it produces a permanent 
palsy of reflex activity. The only explanation of the first lessening of reflex activity 
which is at present plausible is that it is due to stimulation of Setschenow's centre. 

Sedgwick combats this theory just spoken of; he believes that the inhibition 
of the reflexes is such as occurs when a sensitive nerve is galvanized, and is the 
result of a stimulation of the peripheral afferent cardiac pneumogastric nerve- 
endings by the quinine. He bases his theory chiefly on the fact which he has dis- 
covered, that artopine prevents the primary inhibition of reflexes by quinine. This 
is, however, readily explainable without the adoption of the theory of Sedgwick, 
and the results which he obtained after division of the pneumogastrics are scarcely 
in accord with his theory. 

The cause of the permanent influence upon reflex activity has not yet been 
accurately determined, but there is reason for supposing that peripheral sensory 
nerve-endings are first paralyzed. 

Chaperon and Wild found that the motor nerve-trunks are unaffected, but this 
does not prove that the spinal centres are paralyzed, especially as Wild's experi- 
ments seem to show that the nerve-endings in the muscles are attacked. (See 
below.) A. Eulenburg asserts that voluntary movements persist after reflex actions, 
and that the quininized frog will turn into its normal position when laid upon its 
back, although ordinary reflex actions are completely abolished. This, if correct, 
certainly shows that it is either the sensory nerves or the receptive centres of the 
cord whose paralysis by quinine puts an end to ordinary reflex movements. So that, 
accepting the various results reached by experimenters, it is probable that in frogs 
quinine first excites and then paralyzes the peripheral sensitive nervous system. 

Special Senses. — The disorders of special senses caused by quinine 
are due to an action upon the peripheral sense organs; an action 
which is probably directly exerted upon the nerve-structure involved, 
and is not a secondary result of changes in the circulation of the 
organ, although it is still believed by many authorities that the drug 
acts directly upon the aural and retinal circulation. 

In regard to the aural action of quinine, Roosa affirms that large doses of quinine 
cause congestion of the blood-vessels of the middle ear, and in our own observation 
in persons suffering from unilateral chronic inflammation of the middle ear, small 
doses of quinine will produce tinnitus aurium of the diseased ear without affecting 
the sound ear. Again, the fact, long since pointed out by Kirchner, that in the 
lower animals killed with quinine, very great congestion of the middle internal 
ear and the labyrinth, with bloody exudation and in some cases hemorrhage, are 
present after death, has been abundantly confirmed; but Wittmaack, as the result 
of his experimental investigations, believes that these changes are not caused directly 
by the quinine, but are the result of the long drawn out suffocation which precedes 
death. Wittmaack further finds that the ganglionic cells of the cochlear ganglion 
are very distinctly altered by the poison, the anatomical changes being demonstrable 



424 GENERAL REMEDIES 

tour hours after the taking of the fatal dose. He was also able to detect altera- 
tions in the protoplasm in these cells, as the result of chronic poisoning with quinine. 
Analog}' would indicate that as in the retina so also in the peripheral aural 
apparatus, the first effect of quinine upon the circulation is a spasm of the vessels, 
but at present there is no proof of this. The evidence still indicates (not demon- 
strates) that quinine does cause congestion of the peripheral nerve aural apparatus, 
but whether this is or is not preceded by a period of ischemia, and whether it is 
primary or secondary to the action of the drug upon the nerve-endings themselves, 
is undetermined. 

Muscles. — According to the experiments of H. Robert, very large 
doses of cinchonine, and probably therefore of quinine, lessen the 
excitability of the muscles. This is confirmed by the experiments 
of R. B. Wild, who finds that solution of quinine, 1 to 1000, brought, 
in contact with the isolated muscles of the frog, diminishes the irrita- 
bility of the muscle and alters to some extent its relations with stimu- 
lation. The peripheral nerve-endings appear to be more sensitive 
than is the muscle, for when a solution of 1 to 4000 was employed, 
galvanization of the nerve failed to elicit a response, although the 
muscle contracted when the current was applied to it directly. 

Abdominal Organs. — Upon the stomach and intestines quinine 
acts very much as does a simple bitter. In moderate doses it stimu- 
lates digestion and increases the appetite; in large doses it not in- 
frequently causes nausea and vomiting. When there is any morbid 
irritability of the mucous membrane of the stomach or bowels, its 
irritant action is often very marked, and its continued use in large 
doses has been known to cause gastritis. 

The statement of Piorry, that a large dose of quinine would 
produce a distinct immediate lessening of the size of the spleen in 
cases of intermittent fever, appears not to be correct. 

Piorry, Kuchenmeister Hosier and Jerusalimsky have stated that the exposed 
spleen of an animal can be seen to contract when quinine sulphate is injected into 
the stomach, veins, or cellular tissue; but Magendie and Bochefontaine have failed 
in their attempts to produce this asserted contraction. The experiment necessitates 
such abnormal exposure of the organ that only a very pronounced and very con- 
stant diminution could establish the assertion that quinine produces contraction 
of the spleen, and our present knowledge indicates that the alkaloid has no 
immediate decided influence on the size of the organ. 

Circulation. — In ordinary dose, quinine has no effect upon the 
circulation, but as was first shown by Briquet, if given in very large 
quantities it lowers the arterial pressure. The fall of blood-pressure 
appears to be due chiefly to the direct depressant action upon the 
heart muscle or its contained ganglia, but also in part to the action 
upon the walls of the blood-vessels. 

The lowering of blood-pressure, first noted by Briquet, has been confirmed by 
various observers, notably by Schlockow, A. Eulenberg, and Cerna. It lias been 
abundantly proved that the alkaloid thrown into the jugular vein, introduced into 
the coronary artery, or in any way brought in contact with the heart, lessens the 
force and frequency of the pulsations, and finally produces diastolic arrest; also 
that this result is not influenced by separation of the mammalian heart from the 



\\Tiri:i; ionics i_\-, 

nerve-centres, and occurs in the out-ou1 frog's heart. The evidence is conclusive 
thai both in man and in the lower animals qmnme in sufficient amount is a powerful 
depressant to the heart-muscle or ganglia.* 

Schrofi found thai in the quininized animal neither galvanization of a sensitive 

nerve nor asphyxia was able to produce vascular contraction and rise of blood- 

pressure, and Jerusalimsky asserts thai in frogs dilatation of the vessels can be seen.1 
Further, Kobert, experimenting with the excised organs of the warm-blooded ani- 
mals, and Wild, experimenting with the tortoise, prepared according to the method 
of Stevens and Donaldson, have found that very weak solutions of quinine sulphate 
td pari to oOOO) cause enormous dilatation of the vessels, with consequent increased 
rapidity of passage through them of liquid under pressure. It is probable, therefore, 
that the jail <>/ the arterial pressure in poisoning by quinine is in part the result of an 
action upon the vessels. % 

Both Schroff and Jerusalimsky noticed that the fall of arterial pressure produced 
by quinine is preceded by a rise of the pressure, accompanied by an increase of the 
cardiac action. This observation has been confirmed by G. See and Bochel'ontaine; 
but no observer seems to have shown that the rise of pressure is more than a tem- 
porary phenomenon. The primary rise of pressure may be the result of a stimulant 
action upon the vaso-motor centres, as Jerusalimsky found that it was not produced 
after division of the cord. It is not improbable that it is due to disturbances of 
respiration. 

We have never been able to perceive any depressant action upon 
the circulation in man after ordinary therapeutic doses (three to five 
grains) of quinine, and we believe that in tonic doses quinine pro- 
duces no perceptible sedation of the circulation, but that the largest 
ami periodic doses have a distinct influence. § 

Blood. — In 1867 Binz announced that the addition of quinine to 
human blood, in the proportion of one part to 4000, arrests the 
amoeboid movements of the white blood-corpuscles. It has also been 
shown that quinine lessens the diapedesis of the corpuscles through 
the capillaries of frogs. It is questionable how far this effects bears 
any relation to the therapeutic value of the drug.^l 

The present evidence makes it probable that the toxic dose of 
quinine has a demonstrable action upon the white blood-corpuscles, 
but that therapeutic doses have no apparent influence. 

Confirmation of Binz's discovery has been furnished by Scharrenbroich, by 
Kerner, by Geltowsky, and by Jerusalimsky. The minimum effective strength of 
the solution has been found to vary in different species of animals, and even in 
different individuals of the same species. 

* Pantellejeff (Centratbl. f. Med. Wissenach., 1880, xvii. 529) states that atropine will cause 
the heart arrested by quinine to recommence its action. 

t M. Chirone believes that by quinine the heart is arrested in active dilatation. The theory is 
verv improbable. See Rivista Clinica di Bologna, abstracted in Journ. de Pliysint. Norm, ei Patholog., 
1876, *44. 

Heubach, in a series of experiments on the influence of galvanization of a sensitive nerve upon 
the circulation after the exhibition of quinine, failed to detect any paralyzant action of the drug, 
although in some of his experiments the reflex activity was paralyzed. 

| When, in Wild's experiments, the action of quinine was maintained for a length of time, the 
dilatation was finally followed by contraction, which contraction was in all probability the 
outcome of a post-mortem rigidity. 

§ Some studies have been made upon the action of the drug on the capillaries of the brain, 
but the evidence is contradictory anrl insufficient. Consult Psychological and Medico-Legal Journal, 
1875, 33; also Archives of Medicine, i. 33. 

r Binz states that both couiine and camphor act more forcibly upon the white corpuscles out 
of the body than does quinine, and T. Lauder Brunton and Theo. Cash have found that morphine, 
veratrine. and codeine check the ozonizing power of the blood, while digitalin, picrotoxin, and 
caffeine increase it. 



426 GENERAL REMEDIES 

Binz lias studied the mesentery of curarized frogs, to which quinine had been 
given, exposed upon the stage of the microscope. He found that no accumulation of 
white blood-cells in the small vessels, or passages of them out into the tissues, oc- 
curred upon irritation; or, if after a time these phenomena commenced, they were at 
once checked by a small hypodermic injection of the alkaloid. When the inflamma- 
tory process had already commenced in a "Cohnheim frog, "an injection of quinine 
would cause the out -wandering of the corpuscles to cease, and would bring about a 
gradual clearing of the white cells from the choked-up vessels. Binz further took two 
young cats and, after poisoning one of them with quinine, examined their blood. In 
the blood of the impoisoned animal the white cells were far more abundant than in 
that of the poisoned cat. From these facts Binz deduced the conclusion that quinine 
acts destructively in the system upon the white blood-corpuscles, in the same way 
as when they are out of the body. George R. Cutter and H. A. Hare have experi- 
mentally confirmed the effect of quinine in preventing the extrusion of white blood- 
cells from the frog's mesentery, and A. Martin has also found that the action of 
the drug is apparent in the centre of parenchymatous organs, such as the liver. 

Schwalbe * could detect no difference in the blood of a cat before and after 
poisoning by quinine; and the experiments of Geltowsky upon frogs and guinea- 
pigs have yielded similar results: in all his animals after fatal poisoning by the 
alkaloid the movements of the white corpuscles were very active. In a series of 
experiments H. A. Hare found that the vessels in the cinchonized frog were much 
more contracted and had their walls much thicker than in a corresponding frog 
without quinine. This contraction of the vessels is thought by Hare to be the result 
of a direct action exerted by the drug upon the muscular coat of the arterioles. It 
is certain that the alkaloid reduces very markedly the force of the heart. The theory 
that quinine prevents the out-wandering of the blood-corpuscles by lessening the 
force which is driving the corpuscles and at the same time increasing the resistance 
of the capillary walls, seems to us, however, scarcely sufficient; moreover, E. Maurel 
has found that when the minimum fatal dose of quinine is given to the rabbit the 
leucocytes take on the rounded form which is characteristic of the early stage of 
the quinine action in drawn blood. 

Upon the red blood-corpuscles quinine exerts a distinct influence 
in inhibiting their functional activity. 

When blood is drawn from the body and allowed to stand, acid is developed 
in it (see Zunst). Binz beheves that this development of acid is due to oxidation, 
and by an elaborate series of experiments has determined that quinine (also berberine 
sulphate and sodium picrate in almost as great degree) inhibits these changes very 
greatly. These experiments are in accord with the previous ones of A. Schulte: 
the facts may, therefore, be considered proven. 

Binz and his pupil, Ransone, have determined that quinine also inhibits oxidiz- 
ing power of blood as shown by the turpentine-guaiac test, one part of it added to 
a thousand of the mixture delaying the change of color for an hour. In these experi- 
ments Binz used a large number of different salts of quinine, and found that they 
acted identically. He also found that in young cats to which he had given a very 
large but not fatal dose of quinine the freshly drawn blood affected the tincture of 
guaiac much less than it normally should. According to Maurer one per cent, of a 
quinine salt added to fresh blood rapidly destroys the red disks. 

Uterus. — Quinine has been largely used as a uterine stimulant. 
It seems, however, to be well proven that it is not capable of causing 
abortion, that is, of originating uterine contractions, and the only 
evidence of its effect upon this organ is from clinical reports. 

* Quoted by Kerner (Pfluger's Archiv, i. 203). 



WTLI'KRIOniCS 427 

The answer to the question, Has quinine ccbolic qualities? should be made 
out in three ditTerent directions. First, Is there any evidence of quinine produc- 
ing abortion hi healthy women or in females of the lower animals? Second, How 
strong is the evidence of its producing abortion in women suffering from ague? 
Third, What is the evidence in regard to the action of quinine during labor? 

lit regard to the tiist of these sub-questions, the only affirmative evidence we 
have met with is in the experiments of Rancillia, who saw abortion in two bitches 
follow the administration of from six to nine grains of quinine: as the pups in one 
case were already dead before the administration of the drug, it would seem that 
this investigation was not on such a scale as to be at all conclusive. Moreover, we 
have given quinine to two pregnant cats, in one case in sufficient quantity to cause 
death, without disturbing the products of conception. Furthermore, we have met 
with no evidence that quinine is capable of inducing abortion in healthy pregnant 
women. Sayre's case is certainly no proof whatever that quinine will orginate 
labor, as labor had commenced under the influence of the hot and cold douche and 
other measures employed before the quinine was given. Chiara, of Milan, lias fur- 
nished very strong evidence that quinine is incapable of originating uterine contrac- 
tions in healthy pregnant women. In his public service, two doses of a gramme 
(15.34 grains) each were given without effect daily for two successive days to eight 
women, all in the eighth month of pregnancy. It being necessary to cause abortion, 
one gramme was given daily to one woman for seven days, and to another for three 
days, without, in either instance, any effect, so that the labor had to be brought on 
in the usual manner. 

The occurrence of abortion in pregnant women, to whom quinine has been 
given for the relief of malaria, appears to be due to the disease rather than the drug. 
Malaria often induces abortion, and Erwin, James C. Harris, and A. Russwurm 
testify from personal experience that quinine will arrest abortion from such cause. 
J. A. Ashford, Beauchamp,* Rooker,* J. S. May,* and A. d'Arcourd have given 
quinine to hundreds of pregnant women, suffering from malaria, in large doses 
without disturbing the uterus. 

Voluntary Muscles. — C. G. Sauterson, in a series of experiments 
upon both cold- and warm-blooded animals, has found that quinine 
acts directly upon the muscle-fibres, increasing the susceptibility 
and power of the muscle, but, especially in the cold-blooded animal, 
causing it to become fatigued more readily than normal. 

Quinine causes a very marked decrease in the excretion of nitro- 
genous principles. That such decrease is due to diminished formation, 
and not to lessened elimination, seems proved by the fact that in 
Prior's experiments there was no increase of nitrogenous excretion 
beyond the normal following the omission of the quinine. It seems, 
therefore, to be established that quinine has a direct or indirect 
depressing influence upon the tissue-changes of the human organism. 

That the output of uric acid is lessened by quinine has been shown by Ranke, 
by H. V. Bosse and by G. Kerner. The latter observer found that, when about 
nine grains of quinine were taken in divided doses during the course of the day, 
the urea was decreased not quite one-eighth, the uric acid to a little less than one- 
half, the kreatinine was slightly increased, and the nitrogenous material decreased 
about one-ninth. When a very large dose (thirty-eight grains) was taken in the 
morning, the urea and the kreatinine were each decreased about one-fourth, as was 
also the collective nitrogenous material; the phosphoric acid was lessened about 
one-fifth, and the uric acid about four-fifths. Zuntz (quoted by G. Strassburg) 
found that twenty-five grains of quinine reduced his elimination of urea nearly 

* See American Practitioner, 1870. 



128 GENERAL REMEDIES 

forty per cent. A. Schulte also found that 1.8 grammes of quinine depressed the 
elimination by the kidneys thirty-nine per cent; yet in the experiments of Unruh 
the action of the alkaloid in depressing urea elimination was not constant, and in the 
t rials of H. Oppenheim the excretion of urea was actually increased. Nevertheless, 
the experiments, upon the dog, of Rabuteau and of Hermann von Boeck bear strong 
evidence to the fact that quinine does decrease the elimination of urea. 

Contrary to what might have been expected, Strassburg, in an 
elaborate series of experiments, found that quinine had no decided 
effect upon the elimination of carbonic acid either in healthy or in 
fevered rabbits. These observations of Strassburg are opposed by 
those of Bock and Bauer, who found that in cats large doses of the 
alkaloid cause in the first stage of their action lessened carbonic acid 
production, but that when the convulsions appear the carbonic acid 
is increased as the result of the increased muscular activity. R. H. 
Chittenden found that fatal doses of quinine given to fasting rabbits 
had no decided effect upon carbonic acid production until just before 
death, "when both the animal temperature and the excretion of car- 
bonic acid fell distinctly. On the other hand, small doses of quinine 
seemed to cause a gradual falling off in the carbonic acid elimination. 
Although the evidence is somewhat contradictory, it indicates that 
any action of quinine upon carbonic acid elimination must be very 
feeble and uncertain. 

Temperature. — The drift of our present clinical evidence seems 
to indicate that quinine exerts in febrile disease a decided antipyretic- 
action, which is especially manifested during those stages of disease 
in which the natural tendency is towards a lowering of temperature. 
In exanthematous diseases, etc., after the use of the cold bath tw r entj r 
grains of the alkaloid are often efficacious in delajang the return of 
the excessive fever. 

Unless given in enormous toxic doses, quinine does not lower bodily tempera- 
ture in health. It is alleged, however, by G. Kerner and Jiirgensen that it will 
largely prevent the rise of the bodily temperature which normally occurs from 
exercise, and it is asserted by various clinicians that it does not affect the tempera- 
ture in fever. C. Liebermeister came to the conclusion that quinine given in doses 
of from twenty to forty-five grains in one hour is, in typhoid fever, a very active 
and certain antipyretic, a conclusion also reached by the Committee of the London 
Clinical Society. 

Naunyn and Quincke found that sometimes quinine prevented the develop- 
ment of fever after the division of the spinal cord in animals, but in other cases 
failed to do so. Binz has achieved similar results: he says that if the conditions 
of the fever are too favorably constituted the effect of the quinine fails thoroughly. 

Therapeutics. — At present our estimate of the value of quinine 
in disease, and our knowledge of its therapeutic use, rest solely upon 
clinical observation, although recent discoveries have enabled us to 
frame a very plausible explanation of the method by which it 
overcomes malarial disease. 

On account of its power of arresting or preventing putrefactive 
fermentation by killing the microscopic entities which produce such 
changes, Binz has recommended quinine in the so-called septic diseases. 



AUTIPERIODICS 120 

The chief evidence which he produces is in some ten experimenl made upon 
ilofis and rabbits. In each of these experiments two similar animals were poi i 
with putrescent liquids, and to one of the pair quinine was freely administered, in 
two cases the oinchonized animal recovered, while its fellow perished; in three 

experiments neither of the animals died; and in the other five t rials the einel ionized 

animal lived from two to twenty-four hours longer than the other. These experi- 
ments are certainly too lew and indecisive to prove in any degree Binz's view. 
I'o us they indicate very strongly that quinine has no such influence over the dis- 
ease as lu- believes. If living germs in the Mood were really the cause of the septic 
symptoms, and if quinine killed such germs, its action would be as manifest and as 
unmistakable as it is in intermittent, fever. 

The results of Binz's experiments seem to us to agree with the 
emphatic teachings of clinical experience that quinine has no direct 
specific influence in pyemic, septic, or exanthematous diseases. 

As a simple tonic, quinine is largely used, especially in combina- 
tion with iron. We are not entirely convinced that it is of much more 
value in simple debility than is quassia or other simple bitters; but 
if. as is probable, it be true that quinine lessens to a very great extent 
the elimination of nitrogen, — i.e., the consumption of tissue, — the 
general practice is well founded. Hare, as the result of observations 
made upon himself, believes that quinine has a distinct action in 
increasing the formation of the red blood-corpuscles. If this be 
correct, it must have especial tonic value. 

Large doses, sixty to seventy grains, of quinine have been used 
by Briquet and other French physicians in inflammatory rheumatism; 
under these heroic doses the symptoms of inflammatory rheumatism 
have often rapidly abated; but the method has found little favor 
out of France, and is less efficient and more dangerous than other 
plans of treatment now in vogue. In inflammatory rheumatism, after 
the acute symptoms have abated, when the patient shows evident 
sighs of weakness, especially if there be profuse sweating during 
sleep, fifteen grains of quinine daily are often of great service. 

Conceiving the theory that choreic movements may be due to 
weakness of the spinal inhibition, H. C. Wood some years ago 
injected quinine into the veins of choreic dogs, and found that the 
movements were at once arrested by comparatively small doses of 
the alkaloidal salts. This led him to make trial of the remedy in the 
chorea of childhood, and as the result of much experience it has been 
determined that the drug in some cases of this affection is of great 
value. There are certain cases in which enormous doses are borne 
without the production of cinchonism: thus, we have given in a 
month to a child ten years old one thousand grains of the quinine 
sulphate without causing tinnitus aurium or other disagreeable effect, 
but with the result of curing a chorea which had resisted all treat- 
ment for nearly two years. In our experience in the disease, when 
there is no tolerance of quinine no benefit is achieved by its admin- 
istration, but when the quinine is tolerated in large dose its use is 
commonly most beneficial. Led by the results obtained in chorea, 
the chief of H. C. Wood's clinic at the University Hospital, Charles S. 



430 GENERAL REMEDIES 

Potts, conceived the belief that incontinence of urine might in many 
cases be the result of failure of inhibition, and on trial found that 
very large doses of quinine often put an end to this most annoying 
symptom, a result which we can confirm from our own experience. 
Quinine salicylate is often effective in subacute muscular and neuritic 
rheumatism, or in the subsiding stages of acute rheumatism. 

The chief value of quinine is as an antiperiodic. There is at present 
little doubt that the alkaloid does good in all forms of malarial fever 
by directly affecting the malarial Plasmodium or organism. 

Quinine in its relations to vialarial fever may be considered, first, 
as a prophylactic; second, as a curative agent. 

The value of the daily use of quinine to persons exposed to a 
malarial atmosphere has now been thoroughly tested in all portions 
of the world. In North and South America, in Europe, in Africa, and 
in India the prophylactic powers of quinine have been tried on the 
largest scale in connection with the military and naval services, and 
the testimony is unanimous in favor of the drug. 

A single citation will serve to illustrate this fact. J. B. Hamilton reports the 
case of a battery of one hundred and thirty-five men, quartered at Jubbulpore, East 
Indies, in the same barracks with an infantry regiment. Each of the artillerists 
received three grains of quinine every other day: to the infantry none was given. 
The result was that while three hundred out of the five hundred men of the regiment 
were sick at one time with malarial disease, at no period was more than four per 
cent, of the battery affected. 

The dose of quinine as a prophylactic may be considered as two 
grains in the morning and three grains in the evening. 

In intermittent fever, when there is sufficient time, it may be well 
to precede the quinine by a mercurial or other purge. If the expected 
paroxj^sm be so near that there is not sufficient time for the action of 
the purgative, the antiperiodic should be administered without prev- 
ious preparation of the patient. The value of purgatives in obstinate 
intermittents, as an adjuvant to quinine, is often overlooked, 
although in some cases the employment of purgatives, and of such 
diuretics as cream of tartar, seems to be almost essential for the 
successful use of the antiperiodic. 

In pernicious fever, or malignant malarial poisoning, no time should 
be lost after the first paroxysm in getting the patient cinchonized, 
as it may be uncertain whether the attack be of the quotidian or of 
the tertian type. At least sixty grains of the alkaloidal salt should 
be administered during the first twenty-four hours; in very severe 
types of the disease even larger doses than these are necessary, less 
than seventy-five grains of the drug sometimes being unable to 
suppress the disease. 

In remittent or bilious fever it may often be advisable to give 
purgatives and febrifuges before the quinine. As soon as the remis- 
sion has appeared, the exhibition of quinine should be begun. Local 
inflammations or even severe cerebral symptoms occurring during 



ANTIPERIODICS 131 

a remittent fever are no contraindications to the use <>f the specific. 
When gastritis exists, other channels of entrance than the stomach 
should be employed, on account of the local irritant action of quinine. 

When the symptoms in remittent fever are severe and seemingly 
continuous, it may be not only proper hut necessary for the saving 
of life to exhibit quinine freely during (he period of fever. In large 
doses the alkaloid is probably antipyretic as well as antiperiodic, 
ami we do not know of any theoretic or clinical objection to its use 
during the period of fever. 

In malarial intermittent neuralgia, as in all other forms of abnormal 
manifestations of malarial disease, quinine is eflicient, although it is 
usually necessary to administer it in large doses (thirty to forty grains 
at intervals). 

In neuralgia which, although not dependent upon malaria, assumes 
the intermittent type, quinine will often temporarily set aside the 
paroxysmal attacks, and sometimes effect a cure. The same fact 
may be stated in broad terms as true of all non-malarial intermittent 
affections. In the great majority of such cases, unfortunately, the 
action of the quinine is only temporary, and any controlling power 
is soon lost. 

Ordinarily the best method of treating a case of intermittent 
fever is to give the patient a full mercurial purge, and after it has 
acted, to begin the exhibition of the drug about eight hours before the 
expected paroxysm, in doses of five grains every two hours until 
from fifteen to twenty grains are taken; care being exercised to see 
the quinine is in such form as to secure prompt absorption. In cases 
of persistent or chronic intermittent fever, quinine is often admin- 
istered in moderate doses day after day, but we are convinced that it 
is better to use the remedy in large doses at intervals than to admin- 
ister it continuously in smaller amounts. In this climate fifteen 
grains of quinine a day will usually put an end to a mild intermittent, 
but the paroxysm will be likely to recur, even if six grains' of the 
alkaloid be afterwards given daily for some w r eeks. We believe it is 
better to administer from tw r enty to twenty-five grains in the begin- 
ning, sufficient to produce very pronounced cinchonism and to arrest 
the disease at once. The full physiological effect of the drug should 
then be maintained for two or three days, and no more quinine given 
except at certain intervals. The paroxysms have undoubtedly a 
great tendency to return on the seventh day after their arrest, and 
every seventh day for some weeks full cinchonism should be produced. 
If the observation of Councilman, that large doses of quinine entirely 
destroy the malarial organism, be correct, the practice just spoken 
of has a foundation in scientific as well as in empiric observation. 

The general clinical experience, that it is best to administer quinine so that the 
last dose will be given about two hours before the development of the paroxysm, is 
confirmed by the various experiments which have been made upon the relation of 
quinine to the malarial paroxysm. (See Golgi.) Monaco and Panichi believe 
it proven by their experiments, that the results obtained are not due to the quinine 






432 GENERAL REMEDIES 

acting more powerfully upon the young forms of the parasite liberated by tbe pro- 
cesses of segmentation just before the febrile outbreak, but are due to the fact* 
that quinine remains in the blood during the fever, and that the old parasites present 
during the febrile stage arc more susceptible to the action of the quinine than are 
the younger forms, even though the latter be not protected by the red blood-disks. 

Local Use of Quinine. — The effect of quinine upon the lowei 
organisms has suggested its local use in various disorders supposed 
to depend upon the presence of such entities. Thus, Henke, finding- 
some peculiar motile cells in the sputa of whooping-cough, employed 
inhalations of quinine with asserted good results. Henke was not. 
however, the first to suggest either this fungoid pathology of whoop- 
ing-cough or the use of quinine. Binz in 1870 asserted that quinine 
had a specific action in whooping-cough, provided it was given in 
large doses in solution, so as to come in contact with the mucous 
membrane in its passage through the pharynx; and in 1871 Letze- 
rich announced that whooping-cough was due to a fungus in the lung. 
Dawson has confirmed the value of the method of Binz; but, if the 
fungoid theory be — as we do not believe — true, the plan of Henke 
must certainly be the better one. The use in hay-fever, as recom- 
mended by Helmholtz, of a weak tepid solution (one to three grains 
to one fluidounce), as nearly neutral as possible, freely applied to the 
nasal mucous membrane, has not achieved general recognition, and 
any influence which the alkaloid has in either whooping-cough or 
hay-fever probably depends on its direct influence upon the mucous 
membranes. In the later stages of gonorrhoea the topical employment 
of its solution (five to ten grains to one fluidounce) may be 
serviceable.* 

Administration. — Ordinarily quinine is used in the form of 
the sulphate. The powder should be given in capsules, the pill, and 
especially the sugar-coated pill, being prone to become hard and 
uncertain in its solubility and action. If immediate action is required 
the solution may be used, the solubility of the salt being guaranteed 
by the addition of one drop of dilute sulphuric acid to every grain of 
the salt. The quinine hydrochloride is as efficacious as the sulphate, 
and more soluble. 

Hypodermic Use. — Owing to its local irritative action, and the 
insolubility of its ordinary salts, quinine does not lend itself well to 
hypodermic medication. Great local disturbances, abscesses, ulcers, 
and even tetanus, have followed the injection of the sulphate under 
the skin. Many of these manifestations, however, were undoubtedly 
due to lack of proper asepsis. Further, in severe pernicious malarial 
affections, promptness of action is of the greatest importance, and 
many of the German practitioners believe that, hypodermically 
given, quinine acts much more favorably as an antipyretic than when 
given by the mouth. 

* Walerian Sokolow affirms that the local application of quinine to wounds has a very remarka- 
ble effect upon the granulation tissue, a similar effect being produced by the administration of the 
drug by the mouth. (For details, see Jnaag. Dissert., 1891, abstracted in Schmidt's Jahrb., 1892.) 



ANTIPERIODICS 433 

Quinine Bisulphate is soluble in 8.5 parts of water, and is pre- 
ferable to the ordinary sulphate. One gramme (15 grains) of Quinine 
hydrochloride may be dissolved in l C.c. of boiling water, and does 
not precipitate until the temperature roaches LOOT. For hypo- 
dermic injection it is Letter to dissolve the quinine salt, 1 gramme 
in 2 C.c. of water, and give in two injections of 1 C.c. each if ten 
grains are required. According to Gagglio, confirmed by Aufrecht, 
urethan increases the solubility of quinine so that the following 
formula is permanent at ordinary room temperature: Quinine hydro- 
chloride, 0.5 Gm.; urethan, 0.25 Gm.; distilled water, add 5 C.c. 
Quinine hydrobromide is soluble in ten per cent, of water contain- 
ing twenty-five per cent, of alcohol, and its solution has been used 
to a considerable extent hypodermically. 

Contraindication*.— On account of its irritant properties, quinine 
must be used with caution when there is irritability or inflammation 
of any part of the gastro-intestinal tract. It is strongly contraindi- 
cated by inflammation of the middle ear, and may greatly and 
permanently increase dulness of hearing. The statement of M. Fried- 
mann that ergot in. and that of W. B. Dewees that chloral greatly 
lessens the tinnitus aurium produced by quinine and salicylic acid 
need confirmation. Irritability of the bladder or other portion of 
the genito-urinary tract contraindicates the use of quinine: hence 
it is often badly borne by old men. It is even asserted that it will, 
in some persons, cause hematuria.* 

Toxicology. — The first symptoms of cinchonism, as produced 
by full therapeutic doses (ten grains) in man, are usually ringing in 
the ears, slight fulness in the head, and perhaps some deafness. With 
the use of larger doses these symptoms are intensified: the deafness 
is very marked, disturbed vision may exist, and the flushed face, with 
a sense of distention in the head, may point towards a cerebral con- 
ception, which is in some cases relieved by spontaneous epistaxis. 
In decided cinchonism, giddiness and staggering in walking are very 
common. After toxic doses, severe headache, delirium, stupor, 
complete deafness and blindness, dilated pupils, embarrassment of 
respiration, great weakness, convulsions, paralysis, and finally col- 
lapse may result, either comatose or delirious. Quinine deafness 
usually passes off rapidly, but may be permanent. 

More or less complete amblyopia may be produced by quinine 
and end in permanent loss of sight. In most of the numerous 

' In certain regions of country persons suffering from malarial poisons have intermittent 
attacks of hematuria, or probably, to speak more correctly, of methemoglobinuria, in which the 
hematuria has been attributed by many practitioners to the influence of the quinine sulphate. 
The facts, however, that quinine never produces methemoglobinuria in healthy individuals, that 
the attacks are accompanied by chill, fever, and sweat, following, according to Carreau, absolutely 
the course of the paroxysm of intermittent fever, and that, though quinine is used everywhere, 
the methemoglobinuria occurs only in certain localities, certainly seem to prove that the attacks 
are really due to a peculiar form of malaria and not to the quinine. The most elaborate account we 
have met with is that published in Guadeloupe, in 1891, by J. Carreau (La M ethemoglobinurie 
Quinique, 1891; see also Bull. Soc. de Med. Pratique de Paris. 1891; .4 reft, de Med. Navale, 1896, 
lxv., 1897, lxvii.; Bull Therap., xcvii.); Pispiris (Le Progres Med., 1891, xix.) affirms that in some 
cases of malarial fever not only the internal administration but also external friction of the quinine 
sulphate will provoke serious gastro-intestinal hemorrhage. It does not, however, appear probable 
that the quinine in his cases was the cause of the bleeding. 

28 



434 GENERAL REMEDIES 

recorded cases the amount of quinine ingested has been very large, 
but we have seen in one individual twelve grains of quinine repeatedly 
produce temporary blindness. The disturbance of vision may come 
on abruptly or gradually. When fully developed it is usually accom- 
panied by dilatation of the pupils, absence of the light reflex, and 
imperfect response to accommodative effort. There have also been 
noted nystagmus, divergent strabismus, anesthesia of the conjunctiva, 
and increased ocular tension.* 

When the blindness is not complete there is usually pronounced contraction 
of the field, or, in rare cases, scotomata. The disturbance of vision may subside 
with the specific action of the drug, but it may persist for days or months, or even 
permanently. The color-sense is probably first affected; certainly it usually does 
not recover itself until after the return of central vision. The ophthalmoscopic 
examination commonly, but not always, has revealed pallor of the optic disks, with 
excessive lessening in the size of the retinal vessels; indeed, in some cases there 
has been complete obliteration of the vessels of the optic nerve. Graefe has, how- 
ever, noted quinine blindness with normal ophthalmoscopic appearances, while 
Dickinson describes congestion of the retina and chorioid, and Gruening and Mel- 
linger record hyperemia of the disk. The pathogenesis of quinine amaurosis in 
dogs has been studied by Brunner, De Schweinitz, Burabaschew, De Bono, Holden, 
and Druault. The visual disturbances are due to a degeneration of the ganglion 
cells of the retina and the optic nerves, which, with the tracts, finally become com- 
pletely atrophic. The primary lesion is in the nuclei of the cells, where it may be 
demonstrated ten hours after the injection of the drug. The breaking down of 
the least resisting elements of the inner retinal layers — the ganglion cells and nerve- 
fibres — is commonly believed to be caused partly by a lessened blood^supply due 
to spasm of the retinal vessels and partly by a direct action of the drug on the proto- 
plasm of the cells. An ascending atrophy of the optic nerve follows. The spasm 
of the retinal vessels has been attributed to an action of the drug on the vaso-motor 
centres, which is unlikely, and to its influence on the vessel walls or on the 
perivascular vaso-motor plexus. De Bono's theory, that paralysis of the 
neuro-epithelium of the retina causes the amaurosis, has not been confirmed. 

Owing to personal peculiarities or idiosyncrasies, quinine some- 
times causes manifestations entirely unlike those ordinarily seen. 
Thus, in a case reported by A. Erlenmeyer, the symptoms simulated 
those of strychnine-poisoning, f In some persons a few grains of 
quinine produce various forms of dermatitis, the most common of 
which is a scarlatinoid erythema, although urticaria and purpura 
have been reported. (For study of quinine skin eruptions see H. C. 
Wood, Jr.) 

The importance of these idiosyncrasies was shown in a case in our own prac- 
tice, in which two grains given by the mouth produced a furious general urticaria, 
with great subdermal swelling and cardiac depression of the most alarming charac- 
ter; Micciche reports the death of an adult caused by the hypodermic injection of 
seven and seven-tenths grains (one-half gramme), the symptoms being great pale- 

* For discussion of the subject, with resume of the literature, see Toxic Amblyopias, George 
E. de Schweinitz, 1896, and Norris and Oliver's Diseases of the Eye, 1900, iv. 832; for case of blind- 
ness lasting twenty-one days, see Brit. Med. Journ., 1886, i. 823. 

According to Rogers (Journ. Amer. Med. Assoc, 1889), one or two hours after the ingestion of 
twenty grains of cinchonine sulphate there can usually be observed paresis of accomodation, which 
may increase until it becomes almost complete. It seems hardly possible that this phenomenon, 
if an habitual one, could have been overlooked by other observers. 

t For cases, see Brit. Med. Journ., 1869, ii.; Berlin. Klin. Woch., 1877, 294; Phila. Med. 
Times, x. 166; N. Y. Med. Record, xxi. 627. 



ANTIPKRIODICS 435 

dms of tin- surface, small, frequenl pulse, high fever, .severe nervous depression, 
increasing stupor with delirium, great dyspnoea, jaundice, hematuria, and anuria. 
Death occurred on the seventh day. Both during life and at the autopsy the evi- 
dences of great destruction of red blood-corpuscles were apparent. Chevallier 
describes a peculiar a licet ion of the skin, etc., as occurring among workers in the bark. 

Fatal instances of poisoning by quinine are rare in literature, but 
Husemann lias made a collection of cases in which death has been 
attributed to the alkaloid, — not always, in our opinion, with correct- 
ness. The minimum fatal dose is not known, but must be very large. 

Clapton details a case in which a soldier took at one dose an ounce of the sul- 
phate, stirred up in some water, without the induction of any more serious symp- 
tom than a mild stupor; a similar case is mentioned by Lente, on the authority of 
Woodhull; and a third is recorded by Taussig. R. G. Wharton records a case in 
which during thirty-six hours a half-ounce was taken without vomiting and with- 
out ill effect. We cannot help suspecting that in all of these cases much of the drug 
passed through the intestines without absorption. In the famous case of Bazire, 
five ounces taken in the course of ten days caused death. 

Cinchonine Sulphate. — The pure alkaloid cinchonine crystal- 
lizes in prisms and needles. The official cinchonine sulphate is in 
short oblique prisms of a very bitter taste, soluble, at 77° F., in 
fifty-eight parts of water, more freely in boiling water, readily soluble 
in alcohol. 

Physiological Action. — Conzen (quoted by Husemann) has 
found that the action of cinchonine on infusoria and on fermentation 
is similar to but weaker than that of quinine, and that on the move- 
ments of the white blood-corpuscles its influence seems transient. 
It is stated that it is eliminated unchanged and rapidly, the great 
bulk of it being thrown off in the first twenty-four hours. According 
to the experiments of Laborde and Bochefontaine, toxic doses cause 
in the lower animals more violent epileptiform convulsions than do 
the corresponding doses of quinine. In Bochefontaine's experiments 
the relative strength of cinchonine to quinine was about 10 to 16, 
in Bernatzik's (on dogs only) as 4 to 5. De Schweinitz has found 
that cinchonine produces amaurosis in the dog, as does quinine. 

Therapeutics. — As an antiperiodic, cinchonine exerts a similar 
influence to quinine, but is probably about one-third weaker than 
that alkaloid, and must be used in correspondingly larger doses. J. B. 
Hamilton affirms, as the result of experiment, that cinchonine as a 
prophylactic against malaria is even superior to quinine. As a tonic 
we have never been able to perceive that cinchonine acts differently 
from quinine. 

Cixchoxidixe Sulphate occurs in white, silky, lustrous needles 
or prisms, odorless, of a very bitter taste, soluble in sixty-three parts 
of water, freely soluble in acidulated solutions. It polarizes to the 
left, and is not fluorescent. According to See and Bochefontaine, 
cinchonidine produces in the lower animals symptoms similar to 
those caused by quinine, except that the convulsions are less severe. 



436 GENERAL REMEDIES 

A boy aged five years took one hundred and twenty-eight grains 
in solution during six hours without vomiting. There were then 
convulsions followed by great collapse, fall of temperature, pulse- 
lessness (with seventy-four cardiac beats per minute), dilated pupils, 
muscular relaxation, and, finally, death; consciousness was preserved 
to the end.* 

Cinchonidine acts similarly to quinine, but is less powerful, doses 
one-third greater being required. The assertions made by various 
clinicians, that it produces less disagreeable symptoms than does 
quinine, have not been confirmed. De Segrais has found the hydro- 
bromide given hypodermically in doses of four to six grains (0.26-0.4 
Gm.) very efficacious. 

■ Warburg's Tincture. — This is a dark brown liquid, prepared in accordance 
with a very complicated formula,! which has obtained an extraordinary reputation 
in India and other tropical countries in the treatment of severe remittent and malig- 
nant malarial fevers. The testimony is so strong as to its remarkable and almost 
certain efficiency that it cannot be questioned, and entitles the tincture to rank 
above all other remedies. The method of administration is as follows. The bowels 
having been freely opened, a half-ounce of the tincture is given undiluted, all drink 
being withheld, and at the end of three hours a second half-ounce is in similar 
manner exhibited. Soon after the last dose a profuse aromatic perspiration sets 
in, and convalescence is usually secured. The remedy is also commended in one- 
drachm dose in acute nervous exhaustion and collapse without organic disease. 

Quinine Esters. — A number of the esters of quinine have been 
examined pharmacologically, and some of them have found their 
way into practical use. Among these compounds acetylquinine has 
been condemned on account of its taste; benzoylquinine and phos- 
phorylquinine are stated by M. Overlach to be practically inert. 
The esters which have been put upon the market as of value are as 
follows: 

Aristochin. — Neutral carbonic quinic ester. — This tasteless, pinkish-white, 
amorphous powder, soluble in alcohol, ether, chloroform, or glycerin, insoluble in 
water, is said to contain ninety-six per cent, of quinine. According to Stursberg, 
after its ingestion, quinine appears in a short time freely in the urine. It probably 
is effective as an antiperiodic. but has been chiefly commended in whooping-cough 
of children, given in doses of from one to four grains three times a day. 

Euquinine. — The ethylcarbonic ester of quinine has been highly commended 
as a substitute for quinine, and as having the advantage of being practically tasteless 
and of producing a less severe tinnitus aurium. The tinnitus aurium is, however, 
almost certainly a test of the amount of active quinine in the circulation; that 
euquinine is absorbed very slowly and eliminated very slowly is indicated by the 
studies of F. K. Heine, who was unable to obtain from the urine more than seven- 
teen per cent, of the quinine contained in the ingested euquinine. It does not, 
therefore, appear probable that euquinine is as efficient as quinine, but it has been 
commended highly in all forms of malarial disease, also in whooping-cough, chorea, 
anemia, general debility, and, indeed, in all affections for which quinine is gener- 
ally employed. According to Luigi de Carlo, combined with benzonaphthol it is 

* See N. Y. Med. Journ., 1884, xxxix. 

t For complete fomula, see United Stales Dispensatory, 19th ed.; the simplified preparation 
of the National Formulary (Tinctura Antiperiodiea) is the one commonly employed to-day. 



ANTIPER10DICS 437 

especially effective in those tonus of malaria accompanied by intestinal affection. 
Prom fifteen to thirty grains may l>e given in the course of the twenty-four hours. 

SALOQUININE.— This (/tunic ester <>/ suliei/lie aeiil occurs in colorless crystals, 
insoluble in water, but soluble in alcohol and ether. Ii contains fifty per cent, of 
quinine. Overlach alleges that it does not cause cinchonisin; it is, therefore, prob- 
ably as an antiperiodic very feeble, a conclusion which is confirmed by the fact that 
F. K. Kleine was only able to recover during the twenty-four hours from two to 
seven per cent, of the quinine contained in an ingested dose of saloquinine. Never- 
theless, saloquinine lias been most highly commended as an antiperiodic, as an 
antipyretic in fevers, and as an analgesic and antirheumatic in neuralgias, neuritis, 
and similar conditions. It has usually been given in the single dose of thirty grains. 
In sciatica and various neuralgias the dose may be repeated within the twenty- 
four hours. The absorption of the drug appears to be very slow, so that in typhoid 
level thirty grains of it, administered directly after the cold bath, begins to exert 
its influence about the time the effect of the bath is passing off. 

METHYLTHIONINE HYDROCHLORIDE. METHYLENE-BLUE. 

Medicinal methylene-blue (Methylthionince Hydrochloridum) is to 
be carefully distinguished from the dye-stuff, which is a mixture 
of the chlorides of zinc and tetramethylthionine,and contains various 
impurities of which the most important is arsenic. When intended 
for internal use the drug must be free from arsenic and zinc. Parenski 
and Blatteis attribute the various unpleasant symptoms — nausea, 
vomiting, strangury, and the like — which have been reported, to the 
confusion of the medicinal with the dye methylene-blue. 

Absorption and Elimination. — Methylene-blue is readily absorbed 
from both the subcutaneous tissues and mucous membranes of the 
alimentary tract, appearing in the urine, according to Achard and 
Castaigne, within half an hour after its hypodermic injection. Al- 
though the bulk of the drug ingested probabty escapes with the urine, 
the bluish saliva and feces observed by Ehrlich and Leppmann would 
indicate that other glands share in its elimination. 

In a number of morbid conditions the urine does not become 
discolored after the administration of methylene-blue. 

Achard and Castaigne, believing that this was due to failure of elimination, 
suggested the remedy as a test for the permeability of the kidney and reported a 
number of cases of nephritis tending to support their position. Subsequently, 
however, Voisin and Hauser showed that if this colorless urine be warmed, or if 
acetic acid be added to it, the blue color will appear. Achard and Castaigne, in 
reply to this, expressed the opinion that methylene-blue was eliminated in part 
unchanged, and in part as a colorless chromogenic substance, and that the diseased 
kidney permitted the passage of the latter but not of the methylene-blue itself; 
they give, however, no indication of the chemical nature of this chromogen. 

General Action. — Very little is known concerning the physiological 
action of methylthionine. According to Combemale and Francois 
doses of 0.4 gramme per kilo produced in the dog vomiting, purging, 
and diuresis. These observers found that in the guinea-pig 0.3 gramme 
per kilo caused muscular weakness, greatly accelerated respiration, 
and death. After death there was widespread staining of the tissues, 



438 



GENERAL REMEDIES 



especially marked in the nervous system. The blood was choco- 
late-colored and contained methemoglobin. Gautrelet and Gravillat 
state that methylene-blue produces a marked diminution in the 
urinary excretion of nitrogen. 

Therapeutics. — In 1890 Ehrlich and Leppmann called attention 
to the analgesic action of methylene-blue, reporting several cases of 
neuralgic and rheumatic pains relieved by it. Combemale and Fran- 
cois found that while in simple neuralgia it was frequently of service. 





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Fig. 15 — The Effect of Methylene Blue in a Case of Tertian Malaria. 

The continious administration of two grains every three hours led to a rapid but not abrupt 
cessation of the paroxysms with eventual complete cure. 

in neuritis and central nerve-pains it was of little value. Although 
numerous other authors have confirmed the statement that methylene- 
blue possesses some analgesic action, the drug seems to be uncertain 
in its effect, and has no advantage over the newer aniline derivatives.* 
As an antiperiodic, methylthionine deserves a position of high 
rank, rivalling quinine in the treatment of malaria. In four hundred 
and twenty-five cases collected by H. C. Wood, Jr., in which it was the 



• * The theory of Ehrlich that methylene-blue acts as analgesic by staining the axis cylinders 
has been shown by Combemale and Francois to be untrue, for while it is possible to stain living 
tissue with the drug, doses far in excess of those used are necessary. 



ANTIPERIODICS 439 

sole drug employed, there were 85 per cent. (362) of recoveries. Both 
Rosin and Lwanoff have shown that it exerts a direct, destructive 
action on the Plasmodium malaria?. The latter observer states that 
this effect is most marked in the adult forms of the protozoon, in 
this contrasting strongly with quinine (correct (?); see p. 431, small 
print), and that the crescent type, notoriously resistant to cinchona, 
is easily destroyed by methylene-blue. Since it exerts no irritant 
influence on renal structure methylene-blue has been recommended 
especially in the so-called black-water fever. Whenever in a malarial 
disease quinine is contraindicated it is the most serviceable substitute 
we possess. 

Jacobi recommends methylthionine in the treatment of inoper- 
able cancer. Slack has also used the treatment with good results. 

Austin Flint (1895), impressed with the results obtained from the 
use of methylthionine in cases of chyluria, suggested its use in gonor- 
rhea, concluding from its action on the genito-urinary tract that it 
would prove to be a valuable remedy in that affection. The results 
obtained at the hands of many clinical observers do not, however, 
confirm this opinion, experience showing that where the remedy is 
employed alone, and not in combination with well recognized anti- 
blenorrhagic drugs, it has no effect whatever in lessening the ure- 
thral discharge. The property which the drug possesses of coloring 
the urine is, moreover, a distinct disadvantage, as its prevents the 
physician from drawing proper conclusions regarding the natural 
appearance of the urine. Methylthionine may be set down as a mild 
genito-urinary antiseptic of some value in chronic cystitis and pyelitis* 

Administration. — In the treatment of malarial diseases with 
methylthionine it is necessary to continue the use of the drug for 
some time after the cessation of symptoms on account of the liability 
of relapse. From two to three grains (0.1-0.2 Gm.) may be given 
every three hours for ten days, and after this, three grains three times 
a day for a fortnight longer. In gonorrhoea the usual dose is two or 
three grains (0.1-0.2 Gm). three times a day. The remedy may be 
conveniently given in pill form, but preferably enclosed in gelatin 
capsule to avoid the staining of the fingers and lips. The patient 
should always be warned of the probable discoloration of the urine. 

EUCALYPTUS. 

Of the Australian genus Eucalpytus,f which comprises about one 
hundred and thirty-five species of evergreen trees, the U. S. Phar- 
macopoeia recognizes only E. Globulus, whose leaves are official, but 

* This paragraph was written by Prof. H. M. Christian. 

t Attention was first called by Labillaridere in 1792 to the value of the Eucalyptus Globulus 
but it was not until 1860 that M. Ramel commenced the culture of the tree in Paris and induced 
the Prefect of the Seine to order its cultivation on a large scale. Since that time it has been largely 
introduced into Europe, Algeria, South Africa, and California, and in some of these countries planted 
forests are now growing and spreading. The tree is remarkable for combining extreme hardness 
of wood with a rapidity of growth asserted to be about five times that of our ordinary trees; it is 
also affirmed that shingles made of it are fire-proof. Its capability for absorbing and evaporating 
water is extraordinary, and to it has been attributed the freedom of Australia from malarial climatic 



440 GENERAL REMEDIES 

allows the oil of eucalyptus to be distilled from fresh leaves of various 
species of the genus. From the various species of Eucalyptus are 
prepared in Australia a number of volatile oils, and also the Eucaly- 
ptus Gum of the British Pharmacopoeia. The so-called red gum, 
which occurs in commerce in kino-like grains or masses, contains 
nearly five per cent, of tannic acid, and is much used in making 
astringent lozenges. 

Most of the eucalyptus oils are composed very largely of eucaly- 
ptol or of phellandrene. The oils containing phellandrene were thrown 
out by the revisers of the U. S. Pharmacopoeia, evidently under the 
impression that the active physiological portion of the oil is eucalyptol. 
Concerning the physiological action of phellandrene, however, we have 
no knowledge. 

The oil of Eucalyptus (U. S. Pharmacopoeia) is a colorless or 
faintly yellow liquid, of a characteristic, somewhat camphoraceous 
odor and a spicy, disagreeable taste. It is generally considered to 
owe its activity to encalyptol (cineol) of which it contains about 
fifty per cent. It is to be noted that the oil of cajuput contains the 
same active principle in and about the same proportion and is 
probably therefore therapeutically equivalent to the oil of eucalyptus. 

The Oil of Cajuput is obtained from the leaves of Melaleuca 
Leucadendron, a tree growing in the Molucca Islands. This volatile 
oil is of a green color, a peculiar fragrant odor, and a burning, 
camphoraceous taste. 

Official Preparations : 

Fluidextractum Eucalypti 30 minims (2 C.c). 

Oleum Eucalypti 10 to 15 minims (0.6-1.0 C.c). 

Eucalyptol (Cineol) 5 to 10 minims (0.3-0.6 C.c). 

Oleum Cajuputi 5 to 10 minims (0.3-0.6 C.c). 

Physiological Action. — Local Action. — Absorption and Elimi- 
nation. — The oil of eucalyptus is decidedly irritant, large doses caus- 
ing burning in the mouth and fauces, with increased secretion of 
saliva, followed very soon by a feeling of warmth in the stomach. 
It is absorbed from the alimentary canal, and is probably eliminated 
by the lungs, skin, and kidneys. In the experiments of Binz, the day 
after the ingestion of seventy-five drops the breath smelt of the drug 
and the perspiration of amyl alcohol; the urine began to have the 
odor of the oil an hour and a half after its ingestion, and continued 

influences. Indeed, it is stated that a tree will evaporate ten times its weight of water in twenty- 
four hours, and numerous examples are given in which swamps in Europe and Algeria have been 
rapidly converted by it into dry ground. It is believed to destroy malaria not only by draining the 
soil, but also by yielding balsamic exudations to the air; however this may be, there is at present 
very strong evidence as to its power of rendering infected districts healthy. As the consideration 
of this subject belongs to hygiene rather than to therapeutics, the reader is referred for detailed 
information to the following memoirs: Regulus Carlotti (L' Eucalyptus, son Rang parmi les Agents 
de la Matiere Medicate, Ajaccio, 1872), M. Gimbert (L' Eucalyptus Globulus, son Importance en 
Agriculture, en Hygiene, et en Medecine, Paris, 1870), Waterer (Bulletin de la Societe d'Acclimatation, 
1872; London Medical Record, Dec. 1873; London Lancet, 1877, ii.). 

Under the name of Eucalypsinthe, a liqueur distilled from the leaves of the eucalyptus has 
appeared in European commerce. 

It has been affirmed that the leaves of Eucalyptus contain also an alkaloid; but Rabutaue 
kBuII. Therap., lxxxiii. 549) has demonstrated that this is an error. 



ANTIPERIODICS III 

to have it for thirty-six hours, (iimbert states that the odor imparted 
to the urine resembles that of violets, and is very similar to that 
caused by turpentine. Binz affirms that upon the lower infusoria 
the oil acts even more powerfully than does quinine, and its general 
antiseptic properties are decided ((iimbert). 

General Effect. — The constitutional effect of the same dose of the 
oil appears to vary considerably in different individuals; but the 
following summary comprises the facts as nearly as may be. After 
the ingestion of from ten to twenty minims, a period of mental and 
physical activity is often apparent, followed by a feeling of calm and 
serenity. After large doses irritation of the digestive organs some- 
times shows itself by loose stools or even by vomiting. In exceptional 
cases even the moderate dose may produce violent cardiac palpita- 
tion and intense headache and fever, all these symptoms probably 
being due to gastric irritation. Large amounts of the oil cause marked 
depression, with slowing and afterwards quickness and weakness of 
the pulse, general asthenia, sub-normal temperature, blunting of 
sensation, and finally profound loss of muscular power with stupor, 
deepening into unconsciousness, and accompanied by loss of the 
reflexes, and contracted reactionless pupil. 

In anomalous cases the symptoms produced by the oil of eucalyptus differ from 
the typical character. Thus, in an old man who took eighty drops, the power of 
motion almost disappeared; the man also affirmed that he lost for the time being 
all sense of the presence of his limbs, so that he was unconscious of possessing them 
when he shut his eyes, although his intellect was perfectly clear throughout. In 
a case reported by Alfred Neale, a little over half an ounce of the oil of eucalpytus 
is aaid to have produced death in fifteen hours in a healthy boy: the only recorded 
symptoms were violent dyspnoea with collapse.* 

Upon the lower mammalia the oil of eucalyptus appears to act precisely as it 
does on man. According to the experiments of Gimbert, the hypodermic injection 
of the oil is immedately followed by a period of excitement, seemingly in great 
measure due to the intense local irritation; after about half an hour, if the dose 
has been sufficiently large, the animal begins to stumble and totter in walking, the 
breathing grows more and more slow and irregular, the limbs give way, the ears 
droop, the muscular weakness becomes profound, and death, preceded often by 
partial convulsions, occurs through failure of respiration. 

Death appears to be produced by the fatal dose through asphyxia. 
According to the experiments of Gimbert (confirmed by Binz), the 
motor nerves and the muscles are not affected, so that the failure of 
motion and reflex activity is probably due to a depression of the 
motor side of the spinal cord and of the medulla. According to 
Hermann .Schlager, the hypodermic injection of the oil produces a 
temporary rise of temperature, probably as the result of the local 
irritation, but after toxic doses the temperature falls decidedly. 
Schlager also states that the large dose of the oil causes a marked 
lessening of the arterial pressure, whose coming on is not affected 
by previous section of the vagi, by atropinization of the heart or by 

* As a quart of very bloody serum was found in the pleura cavity, and as the boy was not 
seen professionally until he was in articulo mortis, doubt attaches to this case. 



442 GENERAL REMEDIES 

section of the cord. It would appear, therefore, that the oil of eucalyp- 
tus directly depresses the heart or the peripheral arteries. As in 
Schlager's experiments the force of the isolated frog's heart was 
distinctly depressed by the drug, the latter must be a direct cardiac 
depressant. Mosler affirms that in dogs whose spleens were exposed, 
injections of tincture of the leaves of eucalyptus produced a decided 
contraction of the viscus. According to Gimbert, the excretion of 
urea is enormously increased by the drug. 

Therapeutics.— The oil of eucalyptus has some power as an 
antiperiodic, but is much inferior to the cinchona alkaloids and to 
methylene-blue, and should be used only in cases in which for suffi- 
cient reasons these remedies cannot be employed, or as an adjuvant 
to them. 

Joseph Keller used it in four hundred and thirty-two cases, of which two hun- 
dred and ninety-three had suffered from previous attacks. Of the tertians 75.57 
per cent., of the quartans 70 per cent., and of the quotidians 67.89 per cent, yielded 
to the remedy. He recommends it as especially valuable in obstinate cases in 
which quinine has been taken again and again. Lorinser, Haller, Bohn, Carlotti, 
Cortan, Gimbert, Gubler, Tristany, of Spain, J. H. Musser, and others, bear testi- 
mony to the power of Eucalyptus in malarial diseases; while Brudell, Seitz, and 
Papillon affirm it to be of little or no value. 

Oil of eucalyptus is one of the best stimulating expectorants that 
we possess: in both acute and chronic bronchitis it may be exhibited 
when there is free secretion. Children bear it very well. According 
to A. F. Galbraith Faulds, it is valuable in some forms of glycosuria. 
It is also largely used locally as a stimulant antiseptic in various 
chronic inflammatory conditions of the mucous membranes of the 
upper respiratory tract. / 

The oil of cajuput has been used chiefly as an external parasiti- 
cide in various skin diseases, also as a local stimulant application in 
psoriasis, acne, rosacea and pityriasis. It is not very irritating to the 
skin, but is exceedingly destructive to low forms of life, and conse- 
quently has been used as a parasiticide externally, and even internally 
against the Ascarides. In intestinal pain and spasm and in serous 
diarrhoza it is efficient, especially in combination with chloroform, 
camphor, and opium. As a counter-irritant, it has been used in rheu- 
matism; as a stimulant to the skin, in psoriasis, acne rosacea, and 
pityriasis. 

REFERENCES. 

CINCHONA. Binz Pract., 1870, 4. 

, rDB „_ Binz A. E. P. P., 1873. 1. 

Albertoni. . . A. E. P P xy. 2/8. B ixz Amer. Journ. Obst. and Dis. 

Axbertoni and Ciotto. .B. G. T„ xc. 403. f Women, iii. 

Arnaud C. R. A. S., xciii. Bochefontaine. .C. R. A. S., xcvi'. 503. 

Ashford Nat. Med. Journ., Oct. 1871. Boeck and Bauer. . Z. Bi., x. 

Aufrecht T. M., 1903. Bosse In. Dis. Dorpat., 1862. 

Barabaschew. . . .Archiv. f. Augenheilk., 1891, Briquet Traite' therap. de Quinquina. 

xxiii. Heft, 2. Paris, 1855. 

Binz Arch i. Microscop. Anat , Brunton and Cash. .St. Barthol. Hosp. Rep., 

1867, iii. V. A. P. A. 1869, xviii. 269. 

xlvi, 138; A. E. P. P., Burt Med. and Surg. Rep., 1870. 

1873, 1. Cerna P. M. T., x. 493. 

Binz V. A. P. A., 1869, xlvi. 138 Chaperon A. G. P., 1869, 295. 



ANTIPERIODICS 



143 



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Erwin. . . 
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Ophthalmic Rec, 1898, 

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Don W. M. W., 1852. 

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Hark B. M. S. J., cxiv. 73. 

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Keener A. G. P., 1870, iii. 93. 

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161. 

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Kobert A. E. P. P., xv. 49. 

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Landerer Repertorium f. Pharmacie, 

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Letzerich Amer. Journ. Obst., etc., iv. 

761. 
Liebermeister. . . D. A. K. M., 1867, iii. 
London Clinical Society. .Transact., 1870, 

iii. 201. 

Martin In. Dis.. Giessen, 1868. 

Malrel A. M. Ex., 1903, xv. 

Mellinger Klin. Monatsbl. f. Augen- 

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Merkel A. E. P. P., 1902, xlvii. 

Micciche S. Jb., ccxlix. 

Monaco and Panichi. .A. I. B., 1900, iii. 
Monteverid Ann. et Bull, de la Soc. de 

MeUdeGand., May, 1871. 
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Oppenheim A. G. P., 1880, xxxiii. 446. 



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PlORRY. . 

Prior. . . 
Rabuteau. 



C. I. M., 1901. 
A. G. M., 1847. 

A. G. P., xxxiv. 237. 

B. G. T., lxxv., 475. 



Rannonk In, Dis. Bonn., 1871. 

K.m.^v A. J. M. S., 1874. 

Rubswurm American Pract., 1871. 127. 

Sautehmon A. E. I'. P.. 1892. \\\. 

Sayke American Practitioner, 1871, 

260. 
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ScHUi/ra CM. W„ 1871. 

Sedgwick J. P., iii. 22. 

See and BoCHEFONTAINE. .C. R. A. 8., xcvi. 

207; (*. R. A. S., C. 

StRASSBURQ A. E. P. P., ii. 343. 

Stursbohg M. M. W., 1902, xlix. 

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1870, xix. 



FAMILY V.— ANTIPYRETICS. 



Under the term Antipyretics are to be considered certain reme- 
dies which are used in practical medicine for the purpose of reducing 
bodily temperature in fever. Most of these remedies conjoin to their 
antipyretic properties the capability of relieving pain which is not 
due to inflammatory or other distinctly local diseases or traumatism. 




Fig. 16 — To Show how Drugs may Affect Body Temperature. 

H — Heat-regulating center. F — Center for heat formation. D — Center for heat dissipation. 
V — Vaso-motor center. S — Center for sweat glands. C — Capillary blood vessels in the skin. G — 
Sweat gland. T — Tissue cells. Drugs may lower body temperature by diminishing chemical 
activity in T; or by increasing heat dissipation through dilatation of the skin capillaries or greater 
secretion of sweat. 

Some of them are actively antirheumatic. The different members of 
the class vary greatly in the activity of what may be termed their 
secondary properties, some of them being used in reality almost 
entirely as antirheumatics or analgesics, their antipyretic powers 
being inferior for practical purposes to those of other members of 
the group. 

The method in which antipyretics reduce fever temperature has 

not been thoroughly worked out, but it is probable that they exert 

their influence by an action upon the thermogenetic or thermo- 

inhibitory centres. On the other hand, it is possible that they have 

444 



ANTIPYRETICS 145 

such immediate influence on the chemical processes in the various 
tissues of the body as to directly affect the production of heat. 
The question as to \\ hel her it is better in fever to reduce the exces- 
sive temperature by t ho administration of an antipyretic, or by the 
use of the cold bath, is one to which at present a positive answer 
cannot be given. So far as our present knowledge goes the antipy- 
retics produce greater disturbances in the general functions of the 
body than is caused by what we may call the mechanical abstraction 
of heat. Further, the fever process itself is n disturbed condition of 
the nutrition, which is by no means thoroughly comprehended. In 
the administration of an antipyretic we are attempting to modify 
for the better a morbid process of whose real nature we are ignorant 
by the use of a powerful drug of whose action we have not definite 
knowledge. The use of the antipyretics is at present empiric, and in 
our lack of knowledge the cold bath would seem to be a safer remedy 
than the drug. The greater convenience of antipyretics, however, 
exerts a constant pressure for their use by the physician, and little 
by little confidence in them seems to be growing. Our own belief 
is that in minor cases of fever the antipyretic is often superior to the 
cold bath because of its greater ease of application, but that in the 
severe cases of fever, especially when there is a tendency to persistent 
adynamia, the best results are to be achieved by relegating anti- 
pyretics to the class of adjuvants, employing them in moder- 
ate dose simply for the purpose of assisting the cold bath, and 
of pro onging its influence. 

SALICYLIC ACID. 

Salicylic acid occurs in long acicular crystals or in the form of a 
white, dull powder, almost odorless but with a sweetish unpleasant 
taste, accompanied bj r a transient sense of numbness. It is soluble 
at 25° C, in about three hundred and eight parts of water and in 
two parts of alcohol. 

Owing to the irritant action on the mucous membrane salicylic 
acid is very rarely used as an internal remedy. A number of its salts, 
however, are official. Of these the sodium, ammonium, strontium 
and lithium salicylates all occur as white powders with the char- 
acteristic unpleasant taste of salicylic acid, freely soluble in water 
and fairly soluble in alcohol. Besides these salts various esters of 
salicylic acid are also used, of which two are official, methyl and 
phenyl salicylic esters. 

Methyl salicylate is an almost colorless but slightly yellow liquid, 
volatile, with a very penetrating characteristic odor like that of 
wintergreen. It occurs naturally in a large number of plants but is 
especially abundant in the wintergreen and sweet birch. The volatile 
oils of these two last plants contain in the neighborhood of ninety 
per cent, of methyl salicylate to which substance they owe both their 
physical and their therapeutic properties. 



446 GENERAL REMEDIES 

Oil of gaultheria, Oil of Sweet Birch, and the Methyl Salicylate 
prepared synthetically are so similar in composition that they probably 
have the same action upon the human economy, but this is not certain, 
and the apothecary should always put up the exact drug prescribed. 

The question whether the natural salicylic acid of the oil of gaultheria has any 
different physiological action from the artificially prepared but chemically identical 
acid has been elaborately investigated by B. J. Stokvis, who reaches the conclu- 
sion that there is a marked quantitative difference, the natural acid being distinctly 
less poisonous than the artificial, — a circumstance which he thinks is due to the supe- 
rior osmotic properties of the natural acid, causing it to be more rapidly eliminated. 

Salicin is a glucoside obtained from several species of willow and 
poplar. It occurs as colorless crystals without odor and having a 
very bitter taste, soluble in twenty-one parts of water. Its thera- 
peutic virtues depend chiefly upon the fact that it is decomposed 
with the formation of a sugar-like body and salicylic acid. 

It is readily absorbed, and is eliminated as salicin, saligenin, and salicylic acid 
(Husemann). According to Scarpetti, it inhibits the functional activity of the red 
and white blood-corpuscles, but less powerfully than does quinine. It was origin- 
ally introduced in the treatment of specific and acute rheumatism by Maclagan, but 
its therapeutic activity apparently depends upon the salicylic acid which is produced 
out of it in the system; and as its conversion is slow and imperfect, as a remedy it 
is of very inferior value. At present it is rarely used. 

Official Preparations: 

Acidum Salicylicum 5 to 15 grains (0.3-1.0 Gm.). 

Ammonii Salicylas 5 to 30 grains (0.3-2.0 Gm.). 

Lithii Salicylas 5 to 30 grains (0.3-2.0 Gm.). 

Sodii Salicylas 5 to 30 grains (0.3-2.0 Gm.). 

Strontii Salicylas 5 to 30 grains (0.3-2.0 Gm.). 

Phenylis Salicylas f 5 to 15 grains (0.3-1.0 Gm.). 

Methylis Salicylas 5 to 20 minims (0.3-1.2 C.c). 

Oleum Betulae 5 to 20 minims (0.3-1.2 C.c). 

Oleum Gaultheria* 5 to 20 minims (0.3-1.2 C.c). 

Salicinum 15 to 30 grains (1-2 Gm.). 

Physiological Action. — Local Action. — Absorption and Elimina- 
tion. — Pure salicylic acid is so actively irritant to mucous mem- 
branes that its less irritant compounds are universally preferred in 
practical medicine. It is absorbed rapidly through mucous mem- 
branes, and also to a less extent through the skin when applied in 
alcoholic solution (Drasche), or in the form of a soluble compound. 
It circulates as a sodium or other salicylate. Many of its insoluble 
compounds, such as strontium salicylate, bismuth salicylate, etc.. 
undergo slow decomposition in the alimentary canal, yielding their sali- 
cylic acid to the alkaline intestinal juices, and subsequent absorption. 

Salkowski pointed out that salicylic acid in the blood probably exists in the 
form of the sodium salt. Binz supposes that the acid is liberated in the blood by 
the carbonic acid formed in the tissues. Feser and Friedeberger found that unless 



t Phenyl salicylate is considered in connection with phenol (see page G73j 



ANTIPYRETICS 447 

enormous doses of the drug wore injected into the blood so ;is to produce immediate 

violent convulsions and death, no free salicylic acid was demonstrable. In Kohler's 
experiments, when salicylic acid was dissolved in normal blood DO acid was yielded 
to ether; but when the blood of asphyxia — i.e., blood supersaturated with carbonic 
acid was employed, a very notable amount of the acid was extracted by the ether. 
These experiments warrant the conclusion that when the blood is in the normal 
condition the alkaline salicylates are not decomposed by the carbonic acid in it. 

l'Vser and FWedeberger have advanced the theory that the salicylic acid circu- 
lates in the form of an albuminate. This has received some support from the ex- 
periments of Farsky, which seem to show that the acid is capable of forming such 
a compound.* On the other hand, the theory is contradicted by the results of 
Fleischer, who digested albuminous solutions with the acid, and after coagulation 
by heat found all the acid in the filtrate, and who also treated the blood of poisoned 
animals in a similar way, and found the salicylic acid only in the serum, the 
coagulum being free. 

Salicylic acid, although it probably enters into every liquid of the 
organism, escapes from the body chiefly through the kidneys, its 
elimination beginning almost immediately after its ingestion. It 
appears to be excreted partly as salicylic acid and as a salicylate, 
chiefly as salicyluric acid, and partly as, at present, unknown educts. 

Fgolino Mosso recovered from the urine, both in man and animals, practically 
all of the salicylic acid which had been ingested, either in the form of salicylic or 
salicyluric acid. Stockmann found that from one-half to one-twentieth of the 
ingested salicylic acid was eliminated unchanged, the greater portion being con- 
verted into salicyluric acid. Fiirbringer and Drasche failed to detect it in the feces 
the saliva, the bronchial secretion, or the sweat, but Mussy found it in the saliva 
as did also Balz, and Oulmont detected it in the serosity of a blister. It appears in 
the urine very soon after its ingestion, but its elimination proceeds slowly. Thus, in 
a case of exstrophy of the bladder it was detected in the urine dripping from the 
ureter eight and a half minutes after its ingestion (Balz), and it has been found 
in the urine eight days after the exhibition of the last dose (Byanow). The latter 
observer also found it in the urine of a normal man as a salicylate twenty-five min- 
utes after its swallowing. A. E. Stuart, after so small a dose as nine grains of the 
acid, saw free, distinct crystals of salicyluric acid in the urine. It is possible that 
such of the salicylic acid as escapes unchanged from the kidney may, as first ex- 
creted, be in the form of a salicylate, but be set free by the phosphoric acid of the 
urine; at least such would be indicated by the fact that in Balz's case of exstrophy 
sodium salicylate appeared in the urine twelve minutes before the free acid. The 
green color of the urine characteristic of the free use of salicylic acid appears to be 
due to an increase in the formation of indican (S. Wolfberg, M. Robin), or else to 
pyrocatechin (See), and it is not improbable that the pyrocatechin is formed out of 
the salicylic acid. 

Nervous System. — So far as we know, the single, even large, 
therapeutic dose of salicylic acid has no distinct action upon the 
nervous system, unless it be upon the peripheral ends of the auditory 
and perhaps other nerves of special sense, the tinnitus aurium caused 
by it indicating that upon these organs it acts as does quinine. The 
symptoms of salicylic-acid-poisoning indicate that the drug does act, 
when in overwhelming dose, upon the cerebral cortex; how far other 
portions of the nervous system are affected is at present uncertain. 

* He digested various albuminous substances with salicylic acid, washed them with ether until 
it would take no more acid, dried, washed with water, and found on analysis salicylic acid largely 
present in tne residue. 



418 GENERAL REMEDIES 

It is probable that the feeling of depression often produced by the 
free continuous use of the salicylates is largely the outcome of an 
influence upon the cerebral cortex. 

According to See, neither the reflexes nor the general sensibility, nor the con- 
ducting power of the nerve-trunks are sensibly impaired in the lower animals poi- 
soned by a salicylate, but Laborde states that a drachm of the salicylate will produce 
in a dog profound cutaneous anesthesia; and Bochefontaine affirms that in the 
frog the drug depresses the spinal cord, it may be to the point of paralysis. 

Respiration. — The respiratory phenomena produced by salicylates 
in the lower animals are said to be quickening, followed by slowing, 
of the respiration, with gradual failure until death from asphyxia 
results. The slowing and final paralysis are probably due to a direct 
action upon the respiratory centre. The primary quickening has 
been ascribed with plausibility to irritation of the pulmonary vagi, 
though it is probable that there is primary stimulation of the 
respiratory centre. 

When, in Kohler's experiments, the pneumogastrics were divided during the 
period of retardation, the frequency of the respiration was still further lessened. 
Danewsky practised section of the vagi before exhibiting the drug and during the 
first stage of accelerated breathing. In the first instance he found that the breathing 
was only slightly accelerated by the drug; in the second, that the quickened respi- 
ration fell to the same slowness that is seen in the unpoisoned animal with cut 
pneumogastrics. His experiments were too few to be conclusive, but indicate the 
correctness of his deduction. 

Muscles. — According to Charles Livon, salicylic acid has a distinct 
influence upon the muscle-tissue of the frog, producing a primary 
increase and secondary decrease of excitability and altering the 
character of the muscular contractions. 

Circulation. — There was at one time a belief not only among 
clinicians, but also physiologists, that salicylic acid even in small 
doses decreases the arterial pressure. It seems, however, to be estab- 
lished that while toxic doses of salicylic acid do depress arterial 
pressure, moderate doses exert no such influence; indeed, Danewsky 
is probably correct in asserting that they increase the arterial pres- 
sure by stimulating the vaso-motor centres. The final fall of the 
arterial pressure is in large part, if not altogether, due to a direct 
action of the drug upon the heart itself. 

E. Maragliano, in a very large number of sphygmographic and sphygmomano- 
metrical studies, found the arterial pressure usually elevated, and never depressed, 
by therapeutic doses of the drug. In 1879 Hugues Oltremare affirmed that mod- 
erate doses of sodium salicylate increased the frequency of the pulse and the arte- 
rial pressure, and in this was subsequently confirmed by Daneswky. According to 
the latter observer, although the force and energy of the cardiac beat are increased 
by the small dose of the drug, yet the inability of the salicylate to elevate the arte- 
rial pressure after section of the spinal cord shows that the main factor in the rise 
of the blood-pressure is spasm of the blood-vessels due to stimulation of the vaso- 
motor centres in the medulla. Kohler, Oltremare, and Danewsky have found that 
after toxic doses the arterial pressure steadily falls, the heart-stroke becoming 



ANTIPYRETICS 449 

weaker and weaker, and finally being extinguished. Kohler, determining that ( ho 
fall of pressure is not prevented by previous section of the depressors, the vagi, 
and the cervical cord, logically concludes that it is due to an action upon the heart 
itself. In Paul Faval's experiments upon the isolated heart of the frog, small doses 
of salicylic acid had no perceptible influence, although large doses paralyzed the 
viseus. W. Wieohowski, as the result of an elaborate research, believes that sali- 
cylic acid acts specifically upon the brain circulation in causing contraction of the 
blood-vessels, but that this action is not shared by benzoic acid, by aspirin, or by 
the oil of gaultheria. He quotes as concurrent with his conclusion the observations 
of Uhthoff, that salicylic acid produces narrowing of the retinal vessels. 

Digestive Tract. — The indigestion, loss of appetite, and nausea 
which often interfere with the usefulness of salicylic acid and its 
compounds are not due to the irritant action of the drug so much as 
to an influence of the salicylate on the action of the digestive ferments; 
even when the salicylates are not administered during digestion, it 
is probable that they are excreted continuously into the stomach 
and exert their specific action. 

According to Kolbe and others, salicylic acid arrests or prevents the action of 
the non-organized organic ferments. Thus, it will inhibit the action of emulsin upon 
amygdalin or upon myronic acid, and prevent the deyelopment of hydrocyanic acid 
or of the volatile oil of mustard. Miller found that one per cent, of salicylic acid 
was sufficient to check the action of ptyalin upon starch; for the same effect ten 
per cent, of phenol was required. The digestive action of pepsin, outside of the 
body, was very seriously affected by 0.2 per cent, of salicylic acid in Miller's studies, 
but in Kolbe 's experiments the ingestion of twenty grains a day of the drug had 
no demonstrable effect. 

The belief of many clinicians that the salicylates have a distinct 
action in stimulating biliary secretion seems to have a solid experi- 
mental foundation in the researches of H. Moreigne, in the experi- 
ments made upon animals by various observers, and in the observa- 
tions of William Bain and of Pfaff and Balch upon human beings 
suffering from biliary fistula. (See bottom p. 514.) 

Nutrition. — The experiments of Haig, of S. Wolfsohn, of C. Vir- 
chow, of E. G. Salome, of M. Kumagawa, of F. Tausk and B. Vas, 
of Bohland, and of F. G. Goodbody, which have been made upon 
various animals and upon healthy men are so numerous and con- 
cordant in their relations as to prove, despite the contrary result of 
Wiley, that in the normal man or animal salicylic acid and its prepa- 
rations increase to a very great extent the elimination of urea and uric 
acid. In the experiments of Kumagawa, the uric acid was increased 
in the healthy dog from thirty to seventy-four per cent. There was 
also marked increase in the elimination of sulphur compounds, 
although the relation between the elimination of nitrogen and 
sulphur, which in the normal animal is fixed, was distinctly disturbed. 

The question whether the increased elimination of urea and uric acid, produced 
by the salicylic acid, is due to an increased formation of these substances, or is 
simply the outcome of increased activity in elimination, cannot at present be an- 
swered positively. Schreiber and Zandy would seem to be correct in believing that 
there is increased formation of urea, but the experiments of Lecorch6 and Salamon 
29 



450 GENERAL REMEDIES 

indicate tliat in rheumatism the action of the acid is rather in favoring elimination 
than increasing formation. Thus, these observers found that in acute rheumatism 
there is under the influence of salicylates an increase both of urea and uric acid 
usually lasting three or four days, and then followed by a lessening of the excretion 
which in many cases carries the elimination of these substances below the normal. 
If the theory of increased formation of urea and uric acid under the influence of 
salicylic acid be adopted, the question naturally arises as to the method in which 
the drug acts in producing the increased formation. Concerning this we have no 
light at all. 

Closely connected with the subject of the action of the salicylates 
upon nutrition is that of their influence upon temperature. Both in 
the normal man and in the lower animals, except in rare cases, even 
the largest therapeutic doses of the salicylates do not lower the bodily 
temperature (Fiirbringer, Gedl, Danewsky, and See). It is probable, 
however, that salicylic acid, like quinine, has, in non-toxic doses, 
some control over thermogenesis in health. Thus, in one or two 
experiments upon himself, North found that the acid exerted a 
decided influence in preventing the rise of bodily temperature 
normall}'' caused by exercise. 

In fever the antipyretic action of the salicylates is very pronounced ; 
usually in about fifteen minutes after the administration of the drug 
a profuse sweat appears, which is soon followed by a fall of tempera- 
ture that, according to Justi, reaches its maximum in about six hours.* 

The sweating is profuse and exhausting, amounting, according to Ewald, not 
rarely to seven hundred and fifty grammes. The perspiration can scarcely be the 
chief factor in the reduction of temperature, as there appears to be no relation be- 
tween its amount and the degree of the fall, and it usually ceases before the latter 
reaches its maximum. 

In what way the fall of temperature is produced we have at 
present no knowledge, since in the only experiments upon the subject 
— those of Hobart A. Hare, — the doses employed were not sufficient 
to give positive results. 

Especially was this true in the experiments made upon animals suffering from 
fever. Indeed, there was not in those animals any fall of bodily temperature under 
the influence of the salicylic acid administered. To attempt to reason from the 
results reached as to the method of the action of salicylic acid when it does cause 
fall in bodily temperature seems futile. 

SUMMARY. — Salicylic acid, and to a less degree the salicylates, 
are irritant to the mucous membranes, though it is probable that 
the disorder of digestion produced by the acid and its salts is 
chiefly due to their inhibiting the activity of the digestive fer- 
ments. Salicylic acid is readily absorbed and probably circulates 
in the blood as a sodium or other salicylate; it is eliminated 
partly unchanged as a salicylate, partly as salicyluric acid, the 

* The statements in regard to the action of salicylic acid on the pulse in fever vary so much as 
to suggest that when any decided lessening of the cardiacbeat does occur, it is dependent upon the 
fall of temperature. Thus Garcin (Journ.de Therap., 18<t>, 25), Oulmont (Le Prugrcs Med., 187". 
587), and Moeli (Deuisches Archiv, xvii. 592) have all observed the pulse-rate to fall with the fever- 
heat, while L. Schroeder affirms that after moderate doses the pulse is slackened, after large ones 
quickened, and Ewald and other observers state that it is usually not affected. 



ANTIPYRETICS 151 

green discoloration of the urine being due to indican, or perhaps 
to pyrocatechin, which may be an educt from the acid. The elim- 
ination both of urea and uric acid is increased by the salicylates. 
It is probable that this increase is due to some action upon 
general protoplasmic chemical activities, though it may be that 
the salicylates increase chiefly the elimination of formed urea and 
uric acid. In full doses salicylic acid causes symptoms resemb- 
ling those produced by quinine, but after larger doses there are 
mydriasis, marked disturbance of respiration, great nervous pros- 
tration, delirium, dyspnoea, and, if the dose has been large enough, 
death by respiratory paralysis. Moderate therapeutic doses appear 
to have no powerful influence upon the circulation, such physio- 
logical evidence as we have indicating that they increase arterial 
pressure somewhat by exciting the vaso-motor centre and directly 
increasing the cardiac force. In overdoses salicylic acid causes 
fall of the arterial pressure, partly by a direct action upon the 
heart. Our knowledge of the action of the acid upon the nervous 
system is very imperfect, but it seems to be a depressant of the 
motor nervous centres. Moderate doses increase the frequency of 
the respiration, probably in part by an action upon the peripheral 
pneumogastrics, but chiefly by a direct influence upon the respira- 
tory centre. Toxic doses paralyze the respiratory centre. The 
action of salicylic acid upon the temperature of normal man is 
slight and inconstant, unless toxic doses be given; in fever its anti- 
pyretic influence is pronounced, but we have no exact knowledge 
as to the method. 

Therapeutics. — The salicylates were originally introduced by 
E. Butt for the purpose of reducing temperature in typhoid and 
other fevers, but have been superseded by various agents which arc 
not only more effective but more sure and less disagreeable in their 
action. In 1S76 Strieker, of Berlin, using salicylic acid as an anti- 
pyretic in acute rheumatism, discovered the extraordinary anti- 
rheumatic influence of the salicylates, which have come to be the 
standard remedy in all forms of rheumatism. Of all known agents 
the salicylates are possessed of the most power for good in acute 
inflammatory rheumatism, subacute or muscular rheumatism, in 
rheumatic neuritis and other irregular forms of rheumatism, and 
are often temporarily of great service even in chronic rheumatism. 
In gout the powers of the salicylates for good are much less than 
they are in rheumatic diseases, but in all of the irregular forms of 
gouty diseases a salicylate should be tried, and will often be found 
to be of temporary service; they usually combine well with col- 
chicum. Clinical experience has demonstrated that in these various 
conditions the salicylates seem to be palliative rather than curative; 
in other words, that they for the present modify and overcome the 
rheumatic symptoms, but that they exert no permanent influence 
upon the diathesis which is the basis of the disease. In septic 
simulations of rheumatism, such as gonorrhecal rheumatism, and 
in rheumatoid arthritis, the salicylates arc rarely of any service. 



452 GENERAL REMEDIES 

In rheumatic angina and in quinsy, which seems to have some relation 
to the rheumatic diathesis, the salicylates often do good; they are, 
however, of no value in diphtheria. At one time the salicylates were 
used to a considerable extent in chronic cystitis and chronic pyelitis 
for their influence upon the inflamed mucous membrane, but at 
present are rarely employed. 

The salicylates have been used to some extent as antiperiodics, 
but the general drift of experience coincides with that of Helley, who 
found salicylic acid to fail in severe cases of malaria, and to require 
a longer time for the cure of mild cases than does quinine. 

As alterative diuretics the salicylates have been commended by 
Armin Huber and other clinicians in the treatment of acute and 
chronic pleurisy with watery effusions. They have been highly 
commended in diabetes mellitus by Williamson and others. 

Ophthalmic Uses.* — The salicylates are of the greatest value 
in the treatment of iritis, iridocylitis, iridochoroiditis, and, in general 
terms, in uveitis. They relieve the pain of acute and sub-acute glau- 
coma, and even cures of the so-called malignant glaucoma by them 
have been reported by Harry Friedenwald, while the course of 
sympathetic ophthalmia is favorably influenced by them. 

Naturally the promptest results are obtained in rheumatic cases, 
but in inflammations of the uveal tract, not of rheumatic origin, 
they frequently relieve pain and aid in the bringing about of the 
subsidence of the inflammation. They are also effective in certain 
types of interstitial and other forms of keratitis, in herpes of the cornea, 
and in traumatisms of the eyeball, associated with congestion or 
inflammation of the iris and ciliary bodies. 

In order to get the proper results from the salicylates in diseases 
of the eye it is essential that they be used in sufficient dose. Gifford 
believes that most patients are able to take daily one grain of sodium 
salicylate for each pound of weight, without inconvenience. Thus, 
a man weighing 150 pounds should tolerate ten fifteen-grain doses, 
given one and a half hours apart. 

From a very large experience I am sure of the value of the sali- 
cylates in these diseases of the eye, but I have not found it ordinarily 
necessary to use the massive doses advocated by Gifford. His plan 
is to give during the first twenty-four hours eighty to one hundred . 
grains; sixty grains during the next twenty-four hours, and then 
gradually decrease the dose, administering with the salicylates small 
doses of brandy if depression be feared. In my own opinion such 
doses should be reserved for the serious types of ocular inflammations, 
especially sympathetic ophthalmia, acute glaucoma, and iridocyclitis. 
In all cases the local treatment of the disease must not be neglected. 

Attempts have been made to administer the drug subconjunc- 
tival^, but both in man and in rabbits such use is apt to produce 
local necrosis, and in the writer's experiments upon animals there 



* Written by Prof. George E. de Schweinitz. 



ANTIPYRETICS 153 

has been caused a degree of local irritation which has made him unwill- 
ing to make trial of the method upon human beings. The experi- 
ments of Fromaget and Laffay indicate that the solution for 
subconjunctival medication should never be stronger t hau five per cenl . 
So far as 1 am aware intravitreous injections of sodium salicylate 
have not been practised on human beings; although the experiments 
of Schoeler show that in the rabbits they have the power to check 
met astat ic iridocyclitis. 

The studies of Harold Gifford to determine the manner in which 
the salicylates act in diseases of the eye have not led to definite result. 
As Gifford points out, in order for the sodium salicylate to check the 
growth of the ordinary white and yellow pus cocci it requires a solu- 
tion of from 1:1000 to 1:500, so that the bactericidal influence of the 
drug can scarcely be a potent factor in its action. It has been sug- 
gested that the salicylate may cause a local depletion in the inflamed 
area, the arterioles of which have been dilated ad maximum by the 
bacterial toxins by producing a general capillary dilatation. Also, 
that the diaphoresis caused by the drug is an important factor in its 
efficiency; but it must be remembered that other drugs which pro- 
duce capillary dilatation and free sweating are of little value in 
ocular inflammation. 

Use as an Antiseptic. — Salicylic acid was originally brought to 
the notice of the profession on account of its inhibitory influence on 
putrefaction. Kolbe found that 0.04 per cent, had great influence in 
preventing souring of milk. Buchholz states that 0.15 per cent, is 
sufficient to prevent the development of bacteria in ordinary organic 
mixtures, and that the influence of 0.005 per cent, is plainly visible; 
0.3 to 0.4 per cent, of the acid killed bacteria in vigorous growth. 
H. C. Wood, Jr., has shown that neutralization of the acid with 
either sodium or strontium very greatly reduces its germicidal power. 
In the preservation of urine, Meyer and Kolbe found that one part of 
salicylic acid to two thousand parts of urine was sufficient to prevent 
putrefaction. 

There can be no doubt that salicylic acid is capable of accomplish- 
ing much in antiseptic surgery, but it is at present rarely used. 

Salicylic acid has been used to a considerable extent in the pre- 
paration of beer and wine, and for the preservation of various articles 
of food. On February 7, 1881, the French government interdicted 
this use, and in 1885 a commission appointed by the Academy of 
Medicine of Paris, at the suggestion of the Minister of Agriculture, 
reported that it is proved that the prolonged employment of even 
very small amounts of salicylic acid is dangerous, and that in sus- 
ceptible individuals, and especially in aged persons, it is apt to cause 
disorder of digestion and renal disease. 

Locally, salicylic acid is a distinct irritant. In the experiments 
of Hodara its prolonged contact with the skin caused swelling of the 
epidermis, followed after a time by desquamation or exfoliation, the 
cast-off flakes having a thickness in direct proportion to the strength 



454 GENERAL REMEDIES 

of the preparation used. When the application was continued for 
some days oedema and necrosis of the epithelium resulted. It is also 
much used by dermatologists in various skin diseases when there 
is pronounced thickening of the epidermis. 

In 1875 Hirt called attention to the irritation of the pulmonic 
mucous membrane in workmen engaged in the manufacture of salicy- 
lic acid; and various specialists have employed it as a local remedy 
in the treatment of chronic laryngeal and pulmonic inflammations. 

Administration. — The salicylates have been used in rheumatism 
according to two methods. By one, they are given continuously in 
moderate dose; by the other, they are administered in very large 
dose up to the production of cinchonism, then temporarily withdrawn, 
then readministered, and so on until the desired effect has been reached. 
When the symptoms are acute the alternative method of adminis- 
tration is better than the attempt to make the continuous prolonged 
effect; and even in subacute cases of the disease this plan of 
medication is often singularly effective. 

On account of the tendency to interfere with digestion the salicy- 
lates should be administered about two hours after meals, so as to 
get the minimum gastric effect at the time when gastric digestion 
is at its height. Owing to the irritant action of salicylic acid some of 
its preparations are at present always preferred. 

When, however, salicylates are to be employed in large doses, 
they must be given in solution, and should, unless under very excep- 
tional circumstances, be administered in milk. When large closes of 
the salicylates are to be taken, strychnine and often tincture of digitalis 
may be given with them to overcome their depressing effects. The 
Oil of Gaultheria is as prompt in its influence as is the ammonium 
salicylate, and may often be combined with it or used by itself. 

The maximum daily dose of the salicylates may be set down as 
one hundred grains (6.5 Gm.), though in rare cases only is it well to 
give over seventy-five grains (5 Gm.), and usually less will suffice. 
In subacute cases thirty grains (2 Gm.) a day is an average dose. 
The occurrence of tinnitus aurium is an evidence of systemic 
intoxication, and should be the signal for the lessening of the dose. 

Toxicology. — When salicylic acid is given to man in doses just 
sufficient to manifest its presence, symptoms closely resembling 
cinchonism result. These are fulness of the head, with roaring 
and buzzing in the ears. After larger doses, to these symptoms 
are added distress in the head, or positive headache, disturbances 
of hearing and vision (deafness, amblyopia, partial blindness), and 
excessive sweating. According to Reiss, decided fall of temperature 
without alteration of the pulse also occurs; but this is denied by 
other observers. 

The urine may be increased, diminished, or in normal amount, 
during the administration of salicylic acid. After toxic doses it 
becomes albuminous, and See reports a case in which the renal 
irritation was so severe as to give rise to hematuria. 



ANTIPYRETICS 155 

In salicylic-acid-poisoning, along with an intensification of the 
symptoms already mentioned, there are ptosis, deafness, strabismus, 
mydriasis, disturbance of respiration, excessive restlessness passing 
into delirium, slow laboring pulse, leucocytosis, olive-green urine, 
ami involuntary evacuations. In some cases the temperature has 
remained about normal, but in others has approached i lui of collapse. 
The respiration appears to be almost characteristic: if is both quick- 
ened and deepened. In some cases the dyspnoea has been extreme, 
and given rise to the most violent respiratory efforts. Various local 
evidences of vaso-motor weakness may supervene, such as rapidly 
appearing bed-sores at points subjected to pressure, and transitory 
dark-colored maculae on various parts of the body.* 

hi several cases death lias probably been produced by the acid. The most 
conclusive case is thai of II. Quincke. The chief post-mortem changes were a break- 
ing down of the blood, congestion of most of the viscera, and ecchymoses in the 
serous membranes.f 

In rare instances even the therapeutic use of salicylic acid has produced severe 
skin eruptions. The form has been sometimes like the eruptious of urticaria, in 
other cases it has been exanthematous, bullatous, or it has even been purpuric 
and gangrenous.} 

In Borne cases of salicylic-acid-poisoning the mental disturbance has been 
prolonged a week or more. It is stated that upon drunkards the acid acts veiy 
unfavorably, violent delirium being a common and early symptom of its influence. 
There are also some persons whose idiosyncrasies are such that mental disturbance 
is produced even by moderate doses of the acid. In some cases the delirium is 
cheerful, in other it is melancholic in type. In the mildest form it is manifested 
only by a tendency to dream actively and to talk during sleep. In other cases the 
roaring in the ears soon becomes associated with disturbances of vision, which grow 
more marked until the patient not only sees objects in false appearances and colors 
but lias absolute illusions. The hallucinations are apt to take the shapes of animals 
such as are seen in delirium tremens, but there is usually little or no terror, and the 
troops of images may march to beautiful music. In other cases the delirium amounts 
to acute mania, with restlessness, violent outcries, and even a fury of fighting (J. 
Krueg). Mydriasis and amblyopia like that caused by quinine have been noticed 
in a number of cases, but Gibson and Felkin report excessive myosis, with loss of 
the light reflexes. 

Oil of gaultheria is more irritant than the other salicylates, but is 
capable of causing all the ordinary symptoms of poisoning by 
salicylic acid. 

* For cases, consult Deutsches Archiv f. Klin. Med., xix. 319; Centralbl. f. Chirurgie, 1877, 
278, — four hundred and one grains of sodium salicylate taken in twelve hours; London Lancet, 
1876, -', 681; Berlin Klin. Wochenschrift, 1876, No. 4, 8; and Bull. Therap., 1877, xciii. 25. 

t In the case recorded in the Virginia Med. Monthly, June, 1877, forty-eight grains of the acid 
were taken in four hours. The symptoms were violent vomiting, headache, total unconsciousness, 
and stertorous breathing. Death occurred forty hours after the first dose. Our belief is that either 
much more of the acid than forty-eight grains was taken, or, what is more probable, death was 
from some other cause. (.See also Med. and Surg. Reporter, 1878.) The case reported by Dixneuf 
Paris, 1878), also that of Empis and Gubler (Bull, de VAcad. Med. 1877), we have not had 
opportunity to examine. It is worthy of remark that in the early history of the use of the salicylates 
disagreeable symptoms appear to have been present much more frequently than of later years, 
and it is very probable that in many cases such symptoms have been due to the presence of impuri- 
ties. Thus, paracresotic acid has been isolated from commercial salicylic acid by Dunstan. Both 
it and orthocresotic acid have been found by Charteris to be very fatal poisons to the lower animals, 
producing general paralysis and death from asphyxia. One grain of orthocresotic acid and two 
grains of paracresotic acid caused death in three hours in rabbits weighing two pounds (Brit. Med. 
Journ.. 1891, i.). 

XJourn. of Cutaneous and Oenilo-Urin. Diseases, 189G; see especially Deutsch. Med. Woch- 
enschr., 1886. 



456 GENERAL REMEDIES 

An ounce produced violent gastro-intestinal irritation, followed by convulsions, 
coma, and death in fifteen hours, Pinkham. In Juvet's case a half-ounce caused 
death; but the same amount lias been recovered from (Gallaher), probably on f 
account of the vomiting induced. 

Aspirin (Acetyl-salicylic Acid) occurs in white, crystalline, insolu- 
ble needles, of an agreeable taste, which undergo decomposition in 
alkaline fluids with the separation of salicylic acid, and are therefore 
changed by the intestinal fluids. 

Although the urine affords evidence of the presence of salicylic 
acid in half an hour after the ingestion of aspirin, according to Filippi 
and Bufalini, the excretion of the salicylic acid takes place much more 
slowly than when sodium salicylate has been taken. 

Aspirin is undoubtedly capable of acting physiologically and thera- 
peutically as a salicylate. In full doses it produces cinchonism, and 
it may cause disturbances of the digestion and the other disagreeable 
effects of the remedies of the class.* It is, however, usually better 
borne than are the older salicylates, and is probably somewhat more 
continuing in its influence, so that it is especially suitable to the treat- 
ment of subacute and chronic cases, in many of which, when the 
symptoms are not severe, marked benefit may be derived from the 
exhibition of a single dose of the aspirin at bedtime. Like other salicy- 
lates it increases very markedly the elimination of uric acid and other 
nitrogenous excreta (Singer). It appears, however, to have some 
peculiarities in its therapeutic influence; according to Liesan, in 
large dose it acts as a powerful sudorific, and many clinicians are 
concurrent in the statement that both its analgesic and antipyretic 
influences are much more marked than is the case with most salicy- 
lates. It has been used by various clinicians with asserted good 
results to depress temperature in fevers, and has been highly praised 
as a means of subduing pain in migraine, neuralgia, and even in the 
fulgurant agonies of locomotor ataxia. 

Unofficial Salicylic Esters. — A number of esters of salicylic acid have been 
proposed as antirheumatics, especially for the local application. 

Glycerine Salicylate (glycosal) is a white crystalline powder, sparingly 
soluble in water, fairly soluble in alcohol, which is recommended to be applied in the 
form of a twenty-per-cent. alcoholic solution, covered with an impenetrable dress- 
ing and left in place for from six to eight hours. Block uses a twenty-per-cent. 
collodion with asserted success. 

Amyl Salicylate is a colorless liquid, with a salol-like odor, of which one-half 
to one fluidrachm may be applied to rheumatic joints and covered with waxed paper. 

Methyloxymethylsalicylate is a yellow, clear, fluid with a faint peculiar 
odor, mixable with oils. It may be applied diluted with nearly equal parts of olive 
oil; one to three fluidrachms of the mixture applied to the affected part, covered 
with impervious dressing. The application sometimes produces eruptions of the skin. 

* A case has been reported by Otto (D. M. W ., 1903, xxix.) in which aspirin produced violent 
general cedematous erythema, affecting also the mucous membranes, with slightly albuminous 
urine, but no fever and only mild increase in the rapidity of the pulse without irregularity. 



ANTIPYRETICS 157 

s.u.oi'hkm. Aeetylparamidophenyl. Salophen, which contains ■"><>.!) per cent. 
of salicylic acid, occurs in white, crystalline, insoluble Leaflets, and is said to undergo 

decomposition in alkaline solution. Siebel stales thai it yields salicylic acid in the 
alkaline intestinal juices. 

It has Ihhmi largely used in the treatment of all forms of rheumatism, but is 
especially adapted to the subacute and chronic cases. It is capable of producing 
oinchonism and other salicylic acid symptoms, but is less likely to disturb the diges- 
tion than are the older salicylates. Forty-five to seventy-five grains of it (3 4.X. r > 
Qm.) may be given in the course of the day, in divided doses in capsules, or 
better diffused in milk or water. 

ANTIPYRINE. 

Antipyrine or phenyl-dimethyl-pyrazolon, was discovered by Ludwig 
Knorr, of Munich, and first experimented with by Filehne, of Erlangen. 
It is a grayish or reddish-white crystalline powder ,.-of a slightly bitter 
taste, soluble in thirty parts of ether, in less than one part of water, 
and also very soluble in alcohol and chloroform. 

Antipyrina (Phenazonum) 5 to 20 grains (0.3-1.2 Gm.). 

Physiological Action. — Local Action. — The local action of anti- 
pyrine is not thoroughly understood. It is somewhat irritant, and it 
is alleged that it acts with sufficient power upon the sensory nerves 
to be useful as a practical local anesthetic, especially when applied 
to the laryngeal or nasal mucous membrane. It is also stated that 
antipyrine is a very active hemostatic, a forty-per-cent. solution 
causing, when applied locally, most active contraction of all the 
small blood-vessels. 

Saint-Hilaire affirms that the anesthesia produced by antipyrine is complete 
and generally lasts from one to two hours; that the sensibility to touch and also to 
heat and cold is destroyed, the thermal sense returning first; also, that the solution 
must not be of less strength than thirty per cent., twenty-per-cent. solutions having 
no anesthetic effect. Huchard and Henocque (quoted by Armand) state that 
when they cut off the feet of guinea-pigs and put the various stumps into a solution 
of antipyrine, or tincture of ferric chloride, etc., the bleeding was arrested most 
quickly by the antipyrine. 

Absorption and Elimination. — Antipyrine is absorbed with rapidity 
and is eliminated through the kidneys, partly as antipyrine and 
partly as a new substance which is, according to Lawrow, a compound 
of oxyantipyrine with glycuronic acid. 

I. I. Hage was unable to find the drug in the sweat or the saliva, but it lias 
been found in minute quantities in the milk of nursing women both by Pinzani, and 
by Fieux. Armand states that it can be continuously detected in the urine from 
twenty-five minutes to thirty-six hours after its ingestion, although most of it is 
eliminated in the first twelve hours. Perret and C5ivre found that urinary elimina- 
tion begins in the adult or in the child three-quarters of an hour to an hour after the 
ingestion, but that the child eliminates the antipyrine more rapidly than the adult. 
According to Maragliano, the elimination is at its height in four hours, and con- 
tinues for a day and a half. The urine is sometimes increased, sometimes dimin- 
ished, in quantity; it is normal in appearance, and never contains albumin or sugar. 



458 GENERAL REMEDIES 

The theory, that the liver retains or modifies antipyrine, is made more plausible 
by the researches of Wera Iwanoff, who finds that the liver-cells of frogs poisoned 
with antipyrine undergo very pronounced changes in their nuclei and protoplasm. 
The statements of Iwanoff are especially important in connection with the known 
effect of antipyrine upon urea elimination. Disturbances of the hepatic function 
may be at the basis of the inhibitive action of the drug upon urea formation. 

Nervous System. — In sufficient dose, antipyrine is a paralyzant 
to both motor and sensory nerves, although in the human being this 
effect is manifested only after the local application of the drug. It 
is probable, although not certain, that antipyrine also acts upon the 
spinal cord primarily as a stimulant, but in larger quantities, 
secondarily depressing. 

The quietness produced by therapeutic doses of antipyrine and 
the cerebral symptoms of antipyrine-poisoning, show that the drug 
has a peculiar influence upon the cerebral cortex. Simon and Hock 
believe that their experiments prove that the special senses are 
first stimulated and then paralyzed. The convulsions of antipyrine- 
poisoning are probably in part epileptiform (i.e., of cerebral origin) 
and in part tetanic (i.e., of spinal origin), though the testimony 
concerning this matter is contradictory. 

According to the observations of Leon Arduin, Demme, Coppola, Simon and 
Hock, and others, in the frog, in moderate toxic doses (half to one centigramme), 
it causes convulsions, with opisthotonos, and a very marked increase of reflex 
activity. In the earlier stages of this condition the animal is cataleptic, and L. 
Blumeneau affirms that there is a primary stage of quiet with diminished reflex 
activity. If given in overwhelming amount, antipyrine causes in the frog immediate 
quiet, muscular relaxation, with loss of reflex activity, deepening into complete 
paralysis and death. In mammals the chief symptoms of antipyrine-poisoning are 
ataxy, paraplegia, hurried respiration, convulsions with general rigidity, dilated 
pupils, unconsciousness, and fall of temperature, ending in death, which seems 
to be due to failure of respiration. 

Blumeneau and Batten and Bokenham state that section of the cord does not 
prevent the occurrence of the convulsions in the posterior segment of the body; 
while Coppola and Simon and Hock state that it lias such action. Either the first- 
named observers failed to make complete section or else both cerebral and spinal 
convulsions are produced by the drug. 

Chouppe states that the drug even has the power of suspending the strychnic 
convulsions. If the observation of Blumeneau — that in a frog with the cerebral 
hemispheres removed antipyrine produced slowness of reflex reaction, which imme- 
diately disappeared upon section of the spinal cord high up — be correct, the primary 
reflex depression is probably cerebral. 

There seems to be no doubt that antipyrine paralyzes both the motor and the 
sensory nerves. 

Lepine has noticed that if access to a motor nerve be shut off, such nerve, 
after death from antipyrine, will be distinctly more active in its response to stimuli 
than is the implicated nerve; while Simon and Hock noted in frogs killed with 
antipyrine the motor nerves absolutely paralyzed, and have also demonstrated the 
influence of the drug by bringing it in local contact with an exposed nerve. These 
lattei observers further confirm the earlier work of Coppola, and it seems to be 
proved that when applied locally, or given internally, antipyrine is a distinct de- 
pressant of the sensory nerve-trunks. Simon and Hock state that in the beginning 
of the convulsive stage animals can be operated upon without the use of an 
anesthetic. 



ANTIPYRETICS 159 

How far t he vasomotor and other nerves connected with the 
involuntary movements of the body arc influenced by antipyrine is at 
present uncertain, although there is some reason to suspect that the 
drug acts upon them as it does upon the nerves connected with 
voluntary life. 

According to Batten and Bokenham, when locally applied to the exposed intes- 
tine, antipyrine prevents the peristaltic wave which is normally produced by the 
application of common salt, although it does not check the annular contraction at 
the point of irritation; an effect which seems explainable only by the supposition 
thai the intestinal nerves and not the intestinal muscles are paralyzed by the drug. 

Muscles. — According to Devraux-Armand, the muscular stiffness 
of advanced antipyrine-poisoning, when the poisoning is fatal, passes 
directly into post-mortem rigidity. Moreover, in Armand's researches 
the contractions of muscles taken from the body of animals killed 
with antipyrine were much more powerful and prolonged than were 
those produced by the same amount of stimulation in the normal 
muscle. 

Circulation. — Although the effects of antipyrine on the circula- 
tion are of secondary importance, Demme, Arduin, Armand, Henry 
Casimir, and Cerna and Carter have separately determined by experi- 
ment that in moderate doses antipyrine increases the arterial pressure, 
while toxic doses lower the pressiire. The cause or causes of the rise 
have not yet been fully determined; it occurs in curarized animals, 
and is therefore independent of any action of the drug upon the respi- 
ratory centre. According to Cerna and Carter, it is not prevented by 
previous section of the pneumogastric nerves and of the spinal cord, 
and the pulse-w r aves accompanying it are of extraordinary size and 
height. It would appear, therefore, that it is at least in part due to a 
direct stimulation of the heart. Unfortunately, however, the evidence 
which W3 have at present is so contradictory that no positive con- 
clusions can be drawn as to the effect of the largest therapeutic dose 
of antipyrine upon the heart, while in regard to the toxic doses it is 
more than probable that they directly depress the heart. 

Arduin, Demme, Lepine, and Armand all affirm that in the poisoned frog the 
heart is arrested in diastole, but Coppola states that antipyrine has no influence upon 
the circulation in the frog, that in many cases after the largest dose the heart is 
arrested in systole, and that in the Williams apparatus no effect is produced by 
antipyrine upon the isolated heart unless the dose be enormous. Faval found, 
however, that while moderate doses have little effect, large doses diminish the 
frequency and force of the cardiac contractions in the isolated heart of the frog, and 
finally cause diastolic arrest. 

The action of the drug upon the vaso-motor system is at present writing very 
doubtful. Cerna and Carter affirm that it has no influence upon the blood-vessels, 
but give no proof of this; and the fact ascertained by Casimir, that the rise of ar- 
terial pressure is accompanied by a distinct decrease in the size of such vascular 
internal organs as the kidneys, indicates that the drug produces a vaso-motor spasm, 
a view which receives confirmation from the assertion of Arduin, that antipyrine is 
a powerful local hemostatic. On the other hand, Querrolo (quoted by Armand), 
employing the plethysmograph of Mosso, found that the arm is increased in size 



•160 GENERAL REMEDIES 

under the influence of antipyrine, and therefore that the peripheral vessels are 
dilated, and Casimir affirms that similar dilatation can be seen in the blood-vessels 
of the ears of rabbits poisoned by antipyrine. 

The fall of the arterial pressure is without doubt, at least in part, the result of 
a depressing influence of the drug upon the heart itself; but if the observation of 
Bettelheim (quoted by A. Biach), that during the fall of blood-pressure the tem- 
perature of the interior of the body notably falls, while that of the exterior 
correspondingly rises, be correct, vaso-motor paralysis probably is also a factor. 

According to the researches of Cerna and Carter, the pulse is usually increased 
in rate by full doses of antipyrine through a paralytic influence upon the inhibitory 
nerves, but afterwards becomes decreased in number through the direct action of 
the drug upon the heart itself. 

The peculiar lividity often seen in persons under the influence of 
antipyrine is probably due to changes in the blood itself. According 
to Lepine, methemoglobin is largely formed during the poisoning, but 
Crolas and Hagoumeng failed to detect it. The three observers are in 
accord in finding that the number of the red corpuscles is not per- 
ceptibly affected, even by the continuous exhibition of very large doses. 

Temperature. — When given in large doses to the normal animal, 
antipyrine frequently, but not invariably, produces fall in the bodily 
temperature; in the fevered animal this fall is more marked and more 
constant. Its cause is not entirely established, but it is probably 
the result of diminished heat production* through an influence 
exerted directly upon the thermogenetic centres. It is certainly 
independent of any action upon the general circulation, as we have 
seen the temperature of fevered dogs reduced four or five degrees 
by antipyrine without change in the arterial pressure. 

In seven out of nine experiments made by H. C. Wood, E. T. Reichert, and 
Hobart A. Hare upon normal animals, there was a decrease in both the production 
and the dissipation of animal heat. In two experiments both functions were dis- 
tinctly increased. When tetanic convulsions occur from antipyrine there is a marked 
rise of the bodily temperature. In both of the calorimetric experiments in which 
the heat -product ion was increased, very large doses of antipyrine had been given, 
and it is believed that the animal suffered convulsions in the calorimeter. In almost 
all the experiments the decrease of heat-production was very much greater than 
the decrease of heat-dissipation: it would appear, therefore, that antipyrine in the 
normal dog primarily lessens heat-production, the reduction of the heat-dissipation 
probably being the result, at least in part, of the lessened heat-production. In 
experiments upon dogs in which fever had been produced by injections of pepsin, 
both heat -production and heat-dissipation were markedly decreased, but usually 
heat-production was more affected than was heat-dissipation. 

The experiments of Destree and of Engel (quoted by Biach) are, so far as they 
go, in accord with those just given, while Cerna and Carter found pronounced decrease 
of heat-production with simultaneous increase of heat-dissipation in dogs fevered by 
injections of putrid blood. That antipyrine acts through the nervous system is 
strongly indicated by the influence which it has over fever produced by nerve-lesions. 

* The experiments of Gottlieb, however, are not consonant with this view; in three experi- 
ments hypodermic injections of antipyrine were followed by increased heat-production, with a 
greater increase of heat-dissipation and consequent fall of temperature. Similar results were also 
reached in rabbits in which fever had been produced by pricking nerve-centres (Archiv f. Exper. 
Path. u. Pharm., 1891, xxviii.). These experiments are certainly open to the objection that it is 
not shown that the changes in heat-dissipation and production which were noted were really pro- 
duced by the antipyrine, and were not due to the confinement in the calorimeter or to the natural 
variations in the course of the fever itself; in other words, there were no proper control experiments. 



ANTIPYRETICS if, I 

P. J, Martin, R. Gottlieb, and II. (iiranl are in accord in finding thai the rise 
of temperature which is produced in the rabbit by punctures in the neighborhood 
of the striate body is lessoned or altogether put aside by antipyrine. Martin lias 
further found that heat -produet ion is also lessened under these circumstances. 
Gottlieb states that Sawadowski has determined that, in the dog whose spinal 
cord is out lugh up, antipyrine no longer reduces the temperature. 

The studies which have been made by chemists as to t he effects 
of antipyrine upon the elimination of waste products, taken as a 
whole, are in accord with the view that antipyrine lessens heat- 
production. It is indeed true that Chittenden and Cummins were 
uahle to find that antipyrine, either in large or in toxic doses, lias 
any effect upon the elimination of carbonic acid by the animal; but 
before these results can be considered as established further experi- 
mentation is necessary. Again, Armand thought that he had chemi- 
cally proved that antipyrine increases the elimination of urea; but 
the original studies of Umbach, who found that large doses of antipy- 
rine very markedly decreased the elimination of urea, have been so 
abundantly confirmed* that it would seem that it must be considered 
established that antipyrine, both in health and in fever, diminishes 
the output of the nitrogenous products of tissue-waste .f 

Antiseptic Influence. — The influence of antipyrine upon pathogenic 
micro-organisms and upon fermentation has been elaborately studied 
by Engel (quoted by Biach), who found that such influence is so 
exceedingly feeble as to have for practical purposes no existence. 
On the other hand, Chittenden and Stewart state that antipyrine 
inhibits, and if present to the amount of three per cent, stops, the 
digestive action of the acidulated pepsin solution, while Cazeneuve 
and Visbeck find that one per cent, of antipyrine is sufficient to 
indefinitely put off putrefaction of the blood. They also confirm the 
fact that antipyrine is capable of inhibiting the action of ferments 
like pepsin and diastase. Roux and Rodet find that a four-per-cent. 
solution is sufficient to very sensibly affect the Bacillus coli communis. 

SUMMARY. — Antipyrine is absorbed rapidly, and eliminated 
rapidly, at least in part, unchanged. While the ordinary dose of 
antipyrine produces no distinct symptoms, when in large enough 
amount the drug causes languor, malaise, cyanosis, depression of 
the circulation, giddiness, somnolence, epileptiform convulsions, a 
measle-like exanthema, coma, and collapse. Owing to idiosyncrasy, 
it provokes in some cases violent urticaria and subdermal inflam- 
mation, which may be accompanied by fever and other consti- 
tutional disturbances. It is probably a primary stimulant and a 
secondary depressant of the motor spinal cord. It is certainly a 

* Among the chemists who have reached this conclusion by practical experimentation may 
be mentioned Wiczkowski (quoted by Umbach), Walter, of St. Petersburg (Therap. Gaz., ii.j, 
K. Miiller (Jahreab. fiir Thierchemie, xiv.), Ries (quoted by Biach), Albert Robin (Bull. Acad. 
Mid., 1887, xviii.), and Jacubovitsch (Brit. Med. Journ., 1888, ii.). Tausk's (Schmidt's Jahrb., 
cexxxvi.) failure to get a pronounced effect may have been due to his having used too small doses. 

t It would further appear probable that antipyrine alters the normal relation between the 
various excremetitious substances, since Umbach has found that while the urea was markedly 
diminished, uric acid was scarcely altered; and Robin affirms that in his experiments the elimination 
o f uric acid was even augmented. 



462 GENERAL REMEDIES 

paralyzant to both the motor and sensory nerve-trunks, and seems 
to have also some action upon the muscles themselves. A small 
dose may moderately increase arterial pressure, probably by directly 
stimulating the heart and the blood-vessels, although upon these 
points we have no certain knowledge. The final fall of arterial 
pressure is due, at least in part, to a direct action upon the heart. 
In sufficient amount antipyrine causes methemoglobin to appear in 
the blood. It increases the respiratory rate by a centric action. It 
probably lessens the production of animal heat by a direct action 
through the nervous system, independent of any influence upon the 
circulation, and appears also to stimulate heat-dissipation. Both 
in health and in fever it diminishes the output of the nitrogenous 
products of tissue-waste. 

Therapeutic Action. — In fever cases, about half an hour to an 
hour after the ingestion of a full antipyretic dose of antipyrine, profuse 
sweating occurs, and is soon followed by a fall of temperature, which 
is, however, independent of the diaphoresis. 

According to Carl von Noorden, the sweating can be arrested by the use of 
hypodermic injections of atropine or agaricin without affecting the fall of tem- 
perature. Moreover, the sweating is not invariably present, and in dogs, which 
practically do not sweat, antipyrine is a powerful antipyretic in fever. 

According to most authorities, the depression of temperature lasts 
longer than that caused by some other antipyretics, continuing from 
two to ten hours. It is accompanied by a reduction of the rate but 
not usually of the force of the pulse. In some cases the sweating is 
not profuse, and it is probably under such circumstances that observ- 
ers have noticed a markedly increased diuresis. Usually the patient 
is more comfortable under the action of the drug than at other times; 
sometimes, however, there is distressing vomiting. 

Antipyrine may be employed as an antipyretic in almost any 
disease accompanied by high temperature, such as pneumonia, ery- 
sipelas, and typhus, scarlet, yellow, and typhoid fevers, rheumatism, 
etc.; it has also been freely given in the hectic fever of phthisis, but 
various observers state that in such cases it produces so much feeble- 
ness and general depression as to forbid its use: nevertheless, our 
own observation is that when used with caution it often gives great 
relief. In typhus fever it reduces the temperature, but in a number 
of recorded cases it has induced very serious collapse. It appears to 
have some specific action in rheumatism, but does not in this respect 
equal salicylic acid. According to A. Pribram, in pneumonia the 
frequency of the respiration is distinctly lessened by it, but this is 
probably due simply to the lowering of the bodily temperature. In 
children it has been used with asserted good results by a number of 
clinicians, and it appears to be especially useful in the pneumonia 
and bronchitis of the young. 

The second indication for the meeting of which antipyrine is 
sometimes used with success is the relief of motor disturbance. Over 
the minor spasmodic conditions of hysterical origin, over chorea, etc., 



ANTIPYRETICS 163 

antipyrine lias a certain amount of power. In L888 Sonnenberger 
commended it very highly in whooping-cough, stating that if given at 
regular intervals ii greatly lessens the number of paroxysms, or even 
aborts the disease; and further clinical experience seems to show that 
the drug has real value. M. A. Chouppe stales thai antipyrine has 
greal power in relieving uterine pains after parturition or in dys- 
menorrhea, and that if it be given during labor along with ergot it 
allows the contractions to go on, but renders them painless. In more 
severe spasmodic disorders antipyrine sometimes does good. It is 
certainly worthy of trial in tetanus, especially when the temperature 
is high. It may be given in epilepsy with some hope of success, since 
its influence in preventing the return of convulsions is sometimes 
extraordinary, although in the great majority of cases it fails entirely. 
We have studied it in a large number of cases, but are unable to point 
out any indications which will warrant in an individual case an a 
priori opinion that antipyrine will do good. The only method is (hat 
of trial. Not less than forty grains (2.6 Gm.) a day should be given, 
and if. after a time, no cyanosis or muscular weakness mark the 
physiological action of the drug, and the convulsions still recur, the 
dose should be increased up to the physiological limit. The combina- 
tion of antipyrine with ammonium bromide affords much better 
results than either drug alone, and it has become with us a routine 
practice to prescribe in epilepsy a mixture of ammonium and stron- 
tium bromide with antipyrine. We have given to a large number of 
cases fifteen grains (1 Gm.) daily of the antipyrine in this combination 
for many months, and even for years, without cumulative action or 
perceptible effect upon the general nutrition or the general nerve 
functions, except that in some cases, probably by disturbance of 
thcrmogenesis, a condition of such intolerance of cold is produced 
that the drug has to be withdrawn, at least for a time. Antipyrine 
has been used with alleged success in laryngismus stridulus, in nocturnal 
(missions, in asthma, and in urinary incontinence of children. 

The third indication which may sometimes be advantageously 
met by antipyrine is the relief of pain. In April, 1887, See announced 
to the French Academy of Medicine that antipyrine is a powerful 
analgesic, which when given in doses of from forty-five to ninety 
grains (3-5.8 Gm.) a day will control almost all forms of pain. Such 
doses, however, border upon toxic, and are rarely justifiable. More- 
over, they are scarcely ever necessary in properly selected cases. 
Abundant clinical experience has shown that antipyrine for the 
relief of ord : nary inflammatory pains is not reliable, and is in every 
respect inferior to opium; but that it is a very valuable agent against 
various nervous pains, sometimes giving much more relief than does 
opium, and usually causing less disturbance to the system. Espe- 
cially is it effective in rheumatic pains and in migraine and other forms 
of neuralgia in which the pain is the outcome of nerve-storm; it will, 
indeed, often control the pangs of locomotor ataxia; we have even seen 
it abort a gastric crisis. Whether it acts by a true analgesic influence, 



464 GENERAL REMEDIES 

or whether it simply puts aside the nerve-storm which is the cause of 
the pain, is entirely unknown. In violent hemicrania sleep follows 
relief; but antipyrine is not a true hypnotic. Antipyrine is stated 
greatly to increase the analgesic effects of morphine, and is itself, 
in headache at least, made much more effective by caffeine. 

Antipyrine has also been used in various disorders not included 
under the indications already given, often without sufficient reason. 

M. H. Feeny reports subacute Bright' s disease cured by it; Clement, that it is 
of value in bringing about absorption of -pleuritic effusions. Both in diabetes meUitus 
and diabetes insipidus it has been used with asserted good results. Saint-Phillippe 
commends it highly in infantile diarrhoea with indigestion and pain. Salemi affirms 
that it is an active practical antigalactagogue, and in this lias been confirmed by 
Ryan-Tennison and by Guibert. 

Administration. — Antipyrine may be administered hypodermi- 
cally, by the mouth, or by the rectum. The dose for a child of one 
or two years of age may be set down as two to three grains (0.13-0.2 
Gm.); for a child five years old, three to seven grains (0.2-0.46 Gm.); 
for the adult the dose should not exceed twenty grains (1.3 Gm.). 
and ten grains (0.6 Gm.) are usually sufficient, in fever cases, repeated 
every one or two hours until forty grains (2.6 Gm.) are given, or 
sweating comes on, or the temperature falls. 

Hypodermic Use. — Antipyrine has been used to a considerable 
extent hypodermically for the relief of pain, and in neuralgias and 
nerve-pains good can sometimes be achieved by its local influence. 
The burning pain produced by the injection of a thirty-per-cent. 
solution usually lasts only a few minutes, and is not followed by local 
inflammation. Verneuil, however, has reported partial gangrene 
of the foot following and apparently produced by a hypodermic 
injection of antipyrine for the relief of sciatic neuritis. 

Toxicology. — When given to the normal man in doses of from 
ten to twenty grains, antipyrine produces usually no distinct symp- 
toms. If, however, it be administered in a larger dose, and especially 
if it be given in the continuous dose, so as to accumulate in the system, 
it causes languor, malaise, and a peculiar cyanotic pallor of the face, 
with failure of the pulse. Vomiting sometimes occurs. The symptoms 
which have in a number of cases followed large doses are very curious, 
and some of them difficult of explanation. Prominent among these 
symptoms is an eruption on the skin, which may occur without 
constitutional disturbance, but is often accompanied thereby. In its 
most typical form it consists of small, reddish, irregularly circular 
spots, resembling somewhat those of measles, and arranged in patches 
separated by sound skin. The red color usually disappears on pres- 
sure, leaving a brown pigmentation, which also comes into view during 
the fading of the exanthem, and ordinarily continues five or six days. 
In some cases the eruption is erythematous; not rarely it resembles 
an urticaria in which the white wheals may be made very prominent 
by a wide-spread, deep crimson blush. 






ANTIPYRETICS 165 

in a cast- reported !>y Spitz the whole surfaoe of the body was covered with 

bulls, which, becoming continent, involved the skin in a universal desquamative 
inflammation. Very frequently the antipyrine rash is accompanied by wide-spread 
oedema, which may be most pronounced in the extremities, but is especially prone 
to involve the face, causing great swelling, and even closure of the eyes. The mu- 
cous membranes may share in the irritation. Violent catarrhal conjunctivitis is 
not very rare, while corv/.a and laryngitis have been noticed.* 

The marked rise of temperature and disturbance of the circulation which often 
accompany the antipyrine eruption are probably due to the irritation of the skin 
and the subdermal tissue, since, when the antipyretic eruption takes the form of 
an urticaria, the itching, sighing, hysterical unrest, and dyspnoea, which are apt 
to accompany urticarias not due to antipyrine, have been very pronounced. 

In a number of cases of antipyrine-poisoning there have been violent nervous 
symptoms, which seem to be a direct outcome of the action of the poison. The 
vomiting, which is sometimes accompanied by abdominal pain, may be looked on 
as an evidence of local irritation; but this is hardly the case with giddiness, somno- 
lence deepening into coma and passing into profound stertorous unconsciousness, 
with dilatation of the pupils and epileptiform convulsions, — all of which have been 
noted. The unrest, excitement, and violent tremblings not rarely seen seem also 
to be directly produced by the drug. H. M. Briggs reports blackish urine with 
albumin and blood-corpuscles in antipyrine-poisoning. 

As illustrative of the symptoms of unusual forms of antipyrine-poisoning may 
be cited the case reported by F. Spitzer, in which a man, aged twenty-four, shortly 
after taking one hundred and twenty grains of antipyrine during an hour, complained 
of violent pain in the belly, and vomited freely; an hour later he was found in a 
condition of great excitement, screaming, champing his teeth, with a red face, 
much swollen conjunctiva, and cold extremities; the pulse was 108 per minute, 
rhythmical, with strong heart -impulse; the respiration 38. There was precordial 
anguish, pain in the stomach, and marked tremors, with exaggeration of the tendon- 
reflexes. Fifteen hours after the poisoning he was seized with a sudden chill, with 
marked cardiac failure, from which, however, he recovered. 

In another group of cases collapse and cyanosis have been promi- 
nent symptoms. It seems necessary, however, to point out that these 
symptoms in a large proportion of recorded cases seem to have been 
due to constitutional peculiarities of the individual rather than to 
the use of very large doses of antipyrine, and they are rarely attended 
by danger to life. Thus, E. W. Young reports a serious poisoning by 
six grains of antipyrine. Theo. Schwabe reports a case in which 
fifteen grains of antipyrine, given to a young woman for neuralgia, 
produced violent poisoning with collapse, complete amaurosis, 
cyanosis, urticaria, etc. In typhoid and other fevers, fatal depression 
has been produced not infrequently, by doses of antipyrine that were 
not larger than have frequently been used without evil results. Thus, 
in Barrs's case, thirty-five grains of antipyrine were given to a puer- 
peral woman with a temperature of 103.6° F., and followed in three 
hours by half the quantity, after which the temperature sank to 
98° P., and, in spite of stimulation, death occurred thirty-two hours 
later. Our knowledge of the physiological action of antipyrine seems 
to negative the supposition that the depression in these fever cases 
is due to any direct action upon the heart or other vital organ. Heat 
is a stimulant to function, and it may be that the cause of the col- 



* For cases, sec London Lancet, 1881, i.; British Med.Journ., 1888, i.; also 1892, 
30 



466 GENERAL REMEDIES 

lapse is the sudden fall of bodily temperature in a person whose 
nervous system is excessively enfeebled by a fever of typhoid nature. 

Acetopyrine. Antipyrince Acetosalicylas. — This occurs as a white crystalline 
powder, having an odor resembling acetic acid; sparingly soluble in cold, but freely 
in warm water; freely soluble in alcohol, chloroform, and in warm toluol, less so 
in ether and in petroleum -ether. 

It was originally introduced into medicine by Winterberg and Braun as com- 
bining the activities of antipyrine and salicylic acid, into which substances, according 
to W. Meitner, it is broken up in the stomach; the aspirine undergoing further 
decomposition in the intestines. 

Acetopyrine has been much used as an analgesic in migraine, sciatica, neuritis, 
and also as an antipyretic in typhoid and other low fevers. Also as an antirheu- 
matic of especial value in subacute and chronic cases. Its physiological and thera- 
peutic activities are probably those of its constituents. It may be given in doses 
of five to ten grains (0.3-0.6 Gm.) in capsules, or suspended in water, and repeated 
up to thirty grains (2 Gm.) in the twenty-four hours when necessary. In fevers 
two doses may be given two hours apart about the time of the exacerbation. 

ACETANILIDE. 

Acetanilide, antifebrin, or phenylacetamide, is an aniline in which 
one atom of hydrogen has been replaced by the radical acetyl; or 
it may be considered as an ammonia in which one atom of hydrogen 
is replaced by phenol and another atom by acetyl. It is a white, 
crystalline substance, entirely without odor, having a bitter, mildly 
piquant taste. It is soluble, in one hundred and seventy-nine parts 
of water and in two and a half parts of alcohol. 

Official Preparations: 

Acetanilidum 3 to 6 grains (0.2-0.4 Gm.). 

Pulvis Acetanilidi Compositum (Acetanilide 7, 

Caffeine 1, Sodium Bicarbonate 2) 5 to 10 grains (0.3-0.6 Gm.). 

Physiological Action. — Local Action. — According to the experi- 
ments of L. Frothingham and J. H. Pratt, acetanilide is distinctly 
antagonistic to disease germs, scarcely killing them, but markedly 
inhibiting their growth. Applied in the form of powder to a wound 
or mucous membrane, it acts as a stimulant or feeble irritant, a 
desiccant, and probably also as an analgesic. 

Absorption and Elimination. — Absorbed into the blood by some 
unknown method, acetanilide is in great part or altogether converted 
into the paramidophenol sulphate,* and as such escapes from the 
kidney. It is probable that it breaks up in the organism into acetic 
acid and aniline, and that the aniline is then oxidized into paramido- 
phenol, which unites with sulphuric acid.f 

* In an elaborate research on various drugs of the aniline group (Deulsch. Med. Wochensch., 
1895, xxi.) it was found that those substances which produced in the organism paramidophenol 
or paracetamidophenol were active, while those which made elhyl-acetamidophenol were not active. 

t The changes which occur in antifebrin in the system have led to the theory that its medical 
virtues are dependent upon the liberation of aniline in the blood. The symptoms produced by 
antifebrin are certainly similar to those caused by aniline. Thus, Herczel states that in a case of 
aniline-poisoning the symptoms were colossal cyanosis, sweating, vomiting, tinnitus aurium, 
dyspnoea, fixedness of pupils, disturbance of sensibility, and a temperature-fall of 5.3° C, accom- 
panied by a marked decrease in the coloring-matter of the blood and of the number of red 
blood-corpuscles. 



ANTIPYRETICS 167 

Calm and Hepp, however, affirm thai acetanilide eseapea finally with the mine 
in greal part unaltered, and that only a small portion of it is converted into aniline 

and acetic acid; but Midler as well as l'avai Yajna and Kumagawa slate that anli- 
febrin cannot be found in the ni-ine, and consequently that if undergoes entire 
decomposition. Jaffe and Hilbert found that in doss acetanilid passes off chiefly 
as o-oxycarbonol and as paramidophenol, both united with glyco-uronic and .sul- 
phuric acids; in rabbits, chiefly as paramidophenol, paired with the acids. It is 
probable that the proportion of antifebrin which is decomposed varies with the size 
of tin- dose- and the condition of the system. 

Physiological Action. — When given to persons suffering from 
fever in doses of ten grains (0.65 Gm.) acetanilide usually produces 
in about an hour fall of temperature, which reaches its maximum 
in two or three hours and may continue from six to seven hours. 
Usually, but not always, the fall of temperature is accompanied by a 
profuse sweating, which is generally described by clinicians as being 
less than that produced by corresponding doses of antipyrine. The 
fall of temperature is not dependent upon sweating, since it some- 
times occurs without the sweating, and G. Pavai Vajna finds that 
the sweating can be arrested in great part by atropine without 
interfering with the thermic action of the drug. In rare cases the 
lowering of the bodily temperature has been coincident with the 
occurrence of collapse. 

The only information we have concerning the method by which 
acetanilide lowers bodily temperature is furnished by the experiments 
of H. A. Hare and E. M. Evans. It is not sufficient for a positive 
conclusion, but indicates that in fevered animals acetanilide produces 
a fall of the temperature by decreasing heat-production. 

In fifteen experiments upon normal animals, which in nearly all cases were 
allowed to run free, Hare obtained a distinct fall of temperature from acetanilide, — 
a result confirmed by Evans, but not in accord with the results of Cahn and Hepp, 
who found that antifebrin had not a constant influence upon the temperature of the 
normal animal. Hare, employing the calorimeter of H. C. Wood, found that in 
the normal animal heat-dissipation and heat-production were variously affected, in 
some cases being notably increased, in other cases notably decreased, and in others 
not distinctly altered. Evans, employing the D'Arsonval calorimeter, also reached 
various results. In eleven experiments heat-dissipation was decreased nine times, 
while heat-production was increased four times and decreased five times. In ex- 
amining the records of the calorimetric experiments made by Hare and Evans on 
the normal animal, we find that not only did the rectal temperature not full under the 
influence of antifebrin, but in nearly every instance there was a very distinct rise, 
amounting in some cases to over a degree. It is evident, therefore, that these ex- 
periments cannot be used to explain how antifebrin reduces temperature when 
it does cause a fall. The attempt to reason how a certain result is produced by a 
remedy from cx|>erimcnts in which that result was not produced is necessarily futile. 

In Marc's experiments, made upon dogs, in which fever was caused by the 
injection of pepsin, acetanilide failed to produce any constant fall of the bodily 
temperature, probably because the dose was not large enough. In the calorimetric 
studies heat-production was usually decreased, but sometimes if was increased,- — 
an assertion which is also true of heat-dissipation. These experiments must like- 
wise l>e laid aside, because there was no fall of temperature caused by the antifebrin 
In Evans's experiments with fever produced by the injection of albumose, the 
antifebrin nearly always caused a distinct reduction of temperature. In the ealori- 
tnetric studies the results obtained were constant, there being in each of the six 



468 GENERAL REMEDIES 

consecutive experiments a decrease in both the hourly heat -dissipation and the 
hourly heat-production, the amount of decrease seemingly bearing some relation 
to the fall of temperature. It is plain that a decrease of heat-dissipation would 
have a natural tendency to elevate bodily temperature, and therefore the fall of 
temperature must have been due to the decrease of the production, which in turn 
gave rise to the decrease in the heat-dissipation. 

Nervous Syste?n. — The cause of the convulsions of acetanilide- 
poisoning does not seem to have been determined. The coma which 
is present in the advanced stages of the poisoning indicates that, 
directly or indirectly, acetanilide affects the cerebral function, but 
consciousness is stated by experimenters to be preserved at a time 
when the lower portion of the nervous apparatus is distinctly affected. 
According to Bokai, antifebrin paralyzes motor nerve-endings of the 
frog's muscles in a manner similar to curare, and when brought in 
contact with the muscle itself for a sufficient length of time destroy 
its capability of contraction. In the poisoned animal, however, just 
before death the muscles respond actively, although irritation of 
motor nerve-trunks fails to elicit response. 

Circulation. — Usually when acetanilide is given to patients with 
fever there is a fall in the pulse-rate corresponding to the fall of 
temperature. The size of the pulse is also reduced, and it may even 
become thready. Weill has found that, injected into the frog, the 
drug causes at first an acceleration of the heart's beat, with apparent 
increase in the force of the impulses, followed after a time by slowing 
and irregularity of contraction. In the earlier stage the size of the 
pulse- wave is increased and the respiratory curve is more accentuated ; 
later the pulse-oscillations diminish and become irregular and quick- 
ened, and if the dose has been large enough the manometric writing 
resembles that produced by asphyxia. In the earlier stages of the 
action there is a slight rise in arterial pressure. 

The cyanosis of acetanilide-poisoning has been thought to be due 
to the formation of methemoglobin and Stewart reports two cases in 
which the blood had the characteristic chocolate color, although no 
spectroscopic examination seems to have been made. On the other 
hand, in cases of poisoning with marked cyanosis, both Freund and 
Stengel were unable to detect anything abnormal in the blood by 
spectroscopical examination. The blood changes do not appear to 
be characteristic; Stewart reports marked reduction of the number 
of red cells but in one of Stengel's cases the corpuscles were 6,000,000. 
Herczel states that the red corpuscles do not adhere in rouleaux, 
that they are somewhat granular, and that, when the drug is given 
to dogs for a length of time, the blood is less alkaline than normal, 
and contains in its serum dissolved coloring-matter. According to 
Lepine and Aubert, the oxygen of the blood is distinctly decreased. 

Nutrition. — Kumagawa found that while small doses had no 
definite effect, large doses enormously increased the nitrogenous 
elimination; but in Pepine's experiments the results varied, there 
being sometimes an increase and sometimes a diminution, while H. C. 



ANTIPYRETICS 169 

Taylor obtained a slight increase: so that it is impossible al present to 

say what is the action of the drug upon protoplasmic chemical activity. 
According to Kumagawa, acetanilide exerts a strong antiseptic 

influence upon intestinal changes, decreasing the bacteria in the 

intestines, and the urinary indican. 

Therapeutics. — The therapeutic use of acetanilide is exactly 
parallel to that of antipyrine. Some practitioners prefer it on the 
ground that it is less liable than is antipyrine to produce collapse, 
painful skin lesions, or other disagreeable effects, but it is certainly 
capable of causing fatal acute or chronic poisoning. According to 
Sembritski it acts very badly on pregnant or nursing women. Lepine 
affirms that it will relieve not only the fulgurant pains of spinal disease, 
but also the tremors produced by multiple sclerosis, and is often useful 
in epilepsy. 

Acetanilide affords a useful surgical dressing, and has the superi- 
ority over iodoform of being free from odor, and perhaps of being 
more analgesic. It is frequently employed with equal amounts of 
boric acid, finely powdered, in the treatment of minor infected wounds. 
The powder may be freely used, or an ointment of from ten- to forty- 
per-cent. strength; in vaginitis or urethritis a mixture (twenty to 
forty grains to one fluidounce) with gum-arabic water may be injected. 
The free external use is not entirely devoid of danger, as cases have 
been reported of col apse with intense cyanosis and subnormal 
temperature produced by the surgical use of the drug.* 

Toxicology. — The symptoms of acute poisoning by acetanilide are 
vomiting, muscular weakness, cyanosis, coldness of the extremities, 
subnormal temperature, profuse sweating, disturbances of respiration, 
fixed dilated pupils, rapid irregular heart action, ending in collapse 
and cardiac death. In some cases an impaired consciousness has not 
been present until very late in the poisoning; in others a complete 
unconsciousness has been a comparatively early symptom. The 
urine may be dark owing, it is said, to hematoporphyrin (methemo- 
globin?). Leucocytosis with nucleation of the red blood-corpuscles 
has been noted. 

Occasionally there is an eruption somewhat similar to that com- 
monly produced by antipyrine, which is especially abundant upon 
the face and forehead, and of a dark red color. Sometimes the erup- 
tion resembles that of scarlatina, and there may be much subdermal 
swelling (Armin Hugher). Mydriasis and deafness, with ringing 
in the ears, have been noted occasionally. Collapse appears to be 
less frequent than with antipyrine. ^ The experiments of Hobart A. 
Hare show that at present inexplicable cardiac failure may occur 
suddenly. 

In the experiments of Herczel, the symptoms produced by fifteen to twenty 
grains in rabbits were loss of the reflexes, tremors deepening into periodic convul- 

* Sec Med. and Surg. Ren., 1897, lxxvi; P. M. J., Sept. 1901, Herrick and Iron-, ./. A. M. A., 
\lw. p. 351. 



470 GENERAL REMEDIES 

sive movements, great fall of temperature, frequent, irregular, superficial respira- 
tion, retention of urine, coma, and general paralysis, ending, if the dose had been 
large enough, in death, which could not be prevented by artificial respiration. The 
heart was arrested in diastole. After the prolonged action of the drug there was 
fatty degeneration of the heart, liver, and kidneys. Weill noticed, in addition to 
these symptoms, an anesthesia, which in the later stages of the poisoning was almost 
complete. 

Sixty grains of it are asserted to have caused death, but have been 
recovered from after the most alarming symptoms. (See Doll, quoted 
by Biach, also P. Brown.) Marichaux details a case in which 
four grains (0.26 Gm.) caused in a child collapse, with complete 
unconsciousness, ending in recovery. 

In chronic poisoning the most pronounced symptoms are anemia 
and cyanosis; gastric disturbance, failure of the general nutrition, 
rapid, feeble heart action, and distinct enlargement, without tender- 
ness, of the spleen have been noticed. There is not only great decrease 
in the number of the red blood-corpuscles and in the percentage of 
hemoglobin, but also marked increase in the number of the white 
blood-cells, with nucleation of the red blood-corpuscles (see Stengel 
and White). 

ACETPHENETIDIN. 

Acetphenetidin, or Phenacetin, an acetyl derivative of para-amido- 
phenol, crystallizes in tasteless, colorless needles, almost insoluble in 
water, soluble in alcohol. 

Acetphenetidinum — Phenacetin 10 to 20 grains (0.6-1.3 Gm.). 

Phenacetin is eliminated by the kidneys, probably entirely altered, 
phenetidin appearing in the urine. According to Miiller, this change 
must take place after absorption, since both the gastric and pancreatic 
secretions are without effect on the compound. O. Hinsberg and 
A. Kast have found that when given to dogs in doses of fifteen-hun- 
dredths to two-tenths of a gramme per kilo acetphenetidin has no 
effect, but in very large doses it causes vomiting, irregular gait, hurried 
respiration, and somnolence, followed by general cyanosis and 
discoloration of the blood, due to the formation of methemoglobin. 

The therapeutic dose of acetphenetidin produces no symptoms, 
but the toxic dose is said to cause violent vomiting, great cyanosis, 
chocolate-colored urine, yellow discoloration of the body, leucocytosis, 
and death (Kronig). Mahnert states that the muscular weakness 
produced by acetphenetidin is of spinal origin, and that in massive 
doses the drug is antagonistic to strychnine, also that both respiration 
and heart are paralyzed by it. According to the same observer it is 
chiefly eliminated unchanged; and the urine gives a positive Trom- 
mer's reaction, although containing no sugar. Ledoux asserts that 
in doses of 0.5 gramme per kilo acetphenetidin causes a fall of the 
blood-pressure; but as he used an alcoholic solution his results are 
not entirely reliable. H. C. Wood, Jr., and H. B. Wood found that 



ANTIPYRETICS 173 

t ho drug, given intravenously suspended in water, had absolutely 
no effeel on blood-pressure. Doses of 0.5 gramme per kilo killed by 
arrest of respiration; which can, perhaps, however, be attributed to 
the mechanical influence of undissolved particles. Frogs allowed 
fco swim in a saturated aqueous solution of phenaeetin in four hours 
became totally paralyzed, the motor nerves and muscles retaining 
their irritability. Ott found that phenaeetin pronouncedly decreases 
heat-production without producing distinct alteration of blood- 
pressure, and, therefore, probably acts as an antipyretic: by lessening 
the heat-production through an influence upon the nervous system. 
According to Falcone and Gioffredi changes in the cerebral cortical 
cells can be demonstrated in animals killed with phenaeetin. 

Therapeutics. — Aeetphenetidin has been largely used as an 
antipyretic, and for the relief of pains of such character as antipyrine 
is employed against. Large amounts of it can apparently be taken 
without serious result. In a case reported to us by E. C. Wagner, one 
hundred and twenty grains were taken in twelve hours without the 
production of any symptoms. The only serious case of poisoning by 
it. that w r e know of, is that reported by Hollopeter, in which a woman 
took twenty-two and a half grains in six hours, producing collapse 
with marked lividity, great dyspnoea and restlessness, cold perspiration, 
and slightly dilated pupils, ending in recovery.* 

There can be no doubt of the efficiency of aeetphenetidin, and it 
would appear that it more rarely produces unpleasant symptoms than 
antipyrine, though urticaria has been noticed after its exhibition 
(Mahnert). If the statements of Crombie and of Hirschf elder — that 
it acts more gradually than other antipyretics, and that its influence 
does not reach its maximum for three or four hours— be correct, 
aeetphenetidin is probably the most valuable of the antipyretics, 
especially as it seems to be the least poisonous. At present it is 
probably the most used of its class. Phenaeetin is highty commended 
by M. H. Lee as a local antiseptic dressing. 

Phenocoll Hydrochloride. — Phenocoll occurs in white needle-like crys- 
tals; it is made by the action of glycocoll upon phenetidin. Its hydrochloride is a 
wliite, finely crystalline powder, very soluble in water. 

Physiological Action. — The action of phenocoll upon the animal organism 
is not very marked, Von Mering having found that twenty-three grains of it will not 
produce any pronounced symptoms in the rabbit. According to Isaac Ott, the 
toxic dose produces, in the frog, paralysis of both the motor and sensoiy functions 
of the spinal cord, with death from diastolic arrest of the heart; in rabbits, quietude, 
partial paraplegia, and cyanosis, with acceleration of the respiratory movement and 
depression of temperature and of the arterial pressure. David Cerna and William 
S. Carter determined that the influence of phenocoll upon the circulation is 
exceedingly feeble; enormous doses however caused cardiac depression. 

The same investigators affirm that phenocoll has no action upon the blood, but 
the correctness of this seems to be challenged by the cyanosis which has been noted 
both in man and in rabbits. In experiments made upon animals with fever, Cerna 

* Dr. G. Werley in a personal communication has recently given us the account of a fatal case 
of phenaeetin poisoning in a baby of 1 year from 10 grains taken in ten hours. 



472 GENERAL REMEDIES 

and Carter found that the fall of temperature produced by phenocoll is due to an 
enormous reduction of heat-production, heat-dissipation being practically not 
altered. As the result of some evidently not elaborate chemical studies, P. Balzer 
states that phenocoll very distinctly increases the nitrogenous elimination: the 
correctness of this is very doubtful. 

Phenocoll is rapidly absorbed and almost as rapidly eliminated. According to 
Cohnheim, it may be detected in the urine from one to nine hours after its inges- 
tion. It is probably in part oxidized in the system, since the urine after its free 
administration becomes of a dark, reddish-brown color. It is possible, however, that 
this color is due to indican and biliary substances, both of which have been found in 
the urine. 

Therapeutics. — In 1891 Hertel and Herzog stated that phenocoll rarely, 
if ever, produces gastro-intestinal irritation or other disagreeable symptoms, tliat 
its antipyretic action is quick and never accompanied by any depression, and that 
the free sweating which is likely to occur with it may readly be prevented by minute 
doses of atropine. Both Hertel and Herzog assert that phenocoll is a valuable 
remedy in acute and chronic rheumatism. In rare instances it produces vomiting, 
but we have met with no reports of human poisoning by it. The ordinary dose 
may be set down as twelve to fifteen grains (0.78-1 Gm.), in solution or capsule. 

Saliptrin. — Antipyrine Salicylate is a white, coarsely crystalline, odorless, 
slightly sweetish powder, readily soluble in alcohol. It is commended by Guttman 
and Kollmann as an active antipyretic and antirheumatic, which rarely produces 
toxic symptoms, although an eruption resembling that of antipyrine has been noted; 
the color of the urine is not affected, but tests show the presence of a salicylate. 
Kollmann states that it sometimes vomits, and that the daily dose should never 
exceed forty-five grains (2.9 Gm.), and should always be less than this in the be- 
ginning, as some individuals are intolerant of it. Sali pyrin has been used to a con- 
siderable extent in all forms of rheumatism, in influenza, in various fevers, in mi- 
graine, and in the whole class of diseases in which its component constituents have 
been found to be useful; also locally in coryza. The usual dose is from seven to 
fifteen grains (0.45-1 Gm.), in capsule or tablet, repeated every three or four hours 
but some clinicians prefer a single large dose of forty-five grains (2.9 Gm.). 

Pyramidon. — Dimethylamidophenyl-dimethylpyrazolon. — This is a yellowish- 
white, crystalline, almost tasteless powder, soluble in ten per cent, of water. It 
was introduced by Filehne as a remedy having an action similar to that of anti- 
pyrine. It appears to be absorbed readily, and, according to M. Jaffe, is in part 
eliminated unchanged in the urine, in part converted into the red substance, rubaronic 
acid, and in part changed into a substance which is colored deep-blue by ferric chlo- 
ride, and is, probably, antipyrylurea. Its general physiological activities have not 
been worked out, but G. Ssadkowski * is said to have experimentally determined 
that it has a powerful action upon the heart and blood-vessels, increasing the arterial 
tension, so that in cases of tuberculosis of the lungs with already heightened arterial 
pressure, it may produce hemoptysis, and is, therefore, contraindicated. 

Pyramidon has been used to a considerable extent as an antipyretic and as an 
analgesic. The reports as to its value as an antipyretic in typhoid and other low- 
fevers are somewhat contradictory, various clinicians having expressed strong 
sentiments in its favor, claiming that though it acts more slowly its influence con- 
tinues much longer than does that of the older antipyretics. Other observers assert 
that it is more prone than are antipyrine and acetphenetidin to produce excessive 
sweating and collapse. It has been especially praised in migraine, neuralgia, and all 
the pains of the character for which acetphenetidin and antipyrine have been pre- 
viously used. According to Roth, pyramidon is a useful drug in acute rheumatism, 
though of little value in chronic cases. Albrecht has found it of value in asthma. 

* Ssadkowski (Russkij Wratsch, 1902, No. 18). We have not seen the original paper, nor 
yet a satisfactory abstract. 



ANTirVUKTlCS 



17:; 



The dose is twelve grains (0.78 Gm.) dissolved in water or taken in capsules, and 
may, when it is necessary, be repeated up to thirty-six grains (-'.:> Gm.) in the 
twenty-four hours. 

Three compounds of pyramidon have been put upon the market, the camphor- 

ate, the bimm pinnate, and the salicylate. It is affirmed that the presence of cam- 
phoric acid markedly lessens the tendency of pyramidon to produce sweating with- 
out interfering with its antipyretic action. In the bicamphorate the anhydrotic 
inlluence is so great that the drug has been strongly recommended in the night 
sweats in phthisis. 

Pyramidon salicylate appears to be inferior in the treatment of rheumatism to 
the older salicylates, though it may be employed in subacute and chronic cases in 
times of excessive pain. The dose of any one of these preparations is seven and a half 
to twelve grains (0.5-O.7S Gin.), repeated as necessary. In tuberculosis, with exces- 
sive sweating, it is advised to give two doses a day of eight grains (0.5 Gm.) each. 



REFERENCES. 



SALICYLIC ACID. 



\. Hk. xviii. HIS. 

Kin/ I'raet. xxvi. 443. 

Borland Centralb. f. innere Mt*il., 

1890. xvii. 

Birr L. M. It.. 187(5, 193. 

\U i\mv Cb. C, 1877, 809. 

Danewski Vrb. d. Pharra. Lab. Moskau, 

i. 190. 

Drascbe Cb. C, 1870. 

Bwai i) Pract. xvi. 200. 

Faknky Sb. G. W.. lxxiv. ii. 

1a\ ai Thesis, Lyon, 1887. 

Fleischer .Med. Centralb., 1870, 028. 

French Commissions. .B. A. M., 1880, xvi. 
Fromaget and Laffe. .Ann. O.. 1897, cxviii. 
Fcrbringer Zur Wirk. des Salicylsaures, 

Jena, 1875. 

Gallagher Phila. Med. Exam., 1852. 

Gedi C. M. W., 1870, 403. 

Gibson and Felkin. .Pract., 1889, xviii. 
Gifford A. O. R., 1902, xi.; also Tr. 

A. O. S., 1899. 

GOODBOOY J. P. XXV. 

Baig M. C. Tr.. 1888. lxxi. 

Hare T. G., iii. 450. 

Hodara Monats. f. Prakt. Derm.. 

1896 xxiii. 

Houghton A. J. P., 1905, xiii. 331. 

Huber T. G., 1887. 

Justi Cb. C, 1876, 629. 

•IrvKT N. Y. Med. Gaz., 1867. 

Kohi.eh CM. W., 1876, 553. 

Koi.be A. E. P. P., iv. 

Kbueg Wien. Med. Presse, 18S6, 

xxvii. 405. 

Kcmagav. a V. A. P. A., 1888, cxiii. 

l.ABOHDf B. G. T., xciii. 276. 

I.inossif.r and Lannois. . B. G. T., 1890. 

Livon Marseille Me'd., 1890. 

Maragliano Z. K. M., 1884. 

Meyer and Kolbk. .Journ. f. Prakt. Chem. 

xii. 

Moreignk A. M. Ex., 1900, xii. 

M08SO A. E. P. P., xxvi. 

Mussy B. G. T., xiii. 318. 

Xorth Pract. xxiii. 184. 

Oltrf.mahe Thesis, Paris, 1879. 

Pinkham Trans. Mass. Med. Leg. Sue, 

Boston, 1887. 

Quincke B. K. W., xix. 710. 

Reiss B. K. W., 1875, 674. 

Robin L. M. R., 1877, 141. 

Salkowbki B. K. W., 1875, 297. 

Salome Med. Jalirb. Aerzte Wien, 

1885. iv. 
Schreibi.r and Zandy. .D. A. K. M., 18C0, 

lxii. 242. 

See B. A. M., 1877, 697. 

Stockmvx Ed. M. J., Aug. 1906, 103. 



Stokvis 


. Atti d. xi. Congr. Med 




Internazionale, 1894, iii. 


Sthicker 


.B. K. W., 1879, xiii. 


Stuart 


.Pract. xviii. 425. 


Tausk and \ 'as. . 


.S. Jb. cexxxvi. 


Yirchow 


.Z. P.O., vi. 


Wiechowski .... 


.A. E. P. P., 1002, \lviii. 


Wiley 


. Bull. U. S. Dept. Agriculture 


Williamson 


.Pract. 1907, lxxix.136 


WoLFBERG 


.B. A. K. M„ xv. 403. 


Wolfsohn 


.C. M. W., 1877, 30. 


Wood, Jr 


.U. P. M. B., Feb. 1907. 


Wood and Hare 


,T. G., 1886, 73. 


SALICYLIC ESTERS. 






1. YON Nil' 


. 11. T., lxviii. 




ASPIRIN. 


LlESAN 


.D. M. W., 1900. xxvi. 


Singer 


.A. G. P., 1900, Ixxxiv. 




SALICIN. 



Husemann Pflanzenstoffe, 903. 

Maclagan L. 1... 1870. i. 

Scarpetti Rif. M., 1898, 805. 

ANTIPYRINE. 

Arduin Thesis, Paris. 1885. 

Barrs L. L„ Feb. 28, 1885. 

Batten and Bokenham. .B. M. J., 1889, i. 

Biach Die Neuren Antipyretica. 

Hiameneau St. Petersburg Med. Wooh. 

1887. 

Briggs L. M. R., March, 1891. 

Capitan and Gley. .C. R. S. B., 1887, iv. 

Casimib Thesis, Lyons, 1886. 

Cazeneuve and Visbeck. Lyon M. 1892. 
Cerna and Carter. .New Remedies, 1892. 
Chittenden and Cummins. . S. L. P. C. Y., ii. 

Chouppe S. M„ July, 1887. 

Clement Lyon M., 1891. 

Coppol\ Robert's Jahresb., 1885, 314. 

Crolas and Hagoumong. . Lyon M., 1889. 

Demmk Fort. M., 1884, ii. 657. 

Destri' Journ. de Med. Clin, de 

Pharm., 1888, lxxxvi. 
Devreaux-Armand. .Tliesis, Nancv. 18S5. 

Faval Thesis, Lyons, 1887. 

Feeny L. L., 1889. 

Fieux S. Jb. eclvii. 

Filehne Z. K. M., 1884, vii. 641. 

Girard R. M. S. R., 1887, vii. 

Gottlieb A. E. P. P., 1889, xxvi!. 

Gottlieb C. M. W.. 1888. 

Guibert S. M., 1891. 

Hage Robert's Jahresb., 1885. 



474 



GENERAL REMEDIES 



REFERENCES (Continued). 



Iwanoff A. G. P., 1887, Suppl. 

Lawrow Z. P. C, 1901, xxxh. 

Lepine Lyon M., liii. 

Maragliano Kobert's Jahresb., 1885. 

Martin Ott's Modern Antipyretics, 

1891. 
Perret and Givre. .Le Bull. M&l., Aug., 1891. 
Pinzani Gentralb. f. d. ges. Therap., 

Aug., 1890. 

Pribram Prager Med. Woeh., 1884. 

Koux and RoDirr.Lyon M., 1892. 

Saint Hilaire .. .Journ. Laryngol., Otol., etc., 

1892. 
Saint Phillippe .Journ. de Med. de Bordeaux, 

1891. 

Schwabe Deutsche Med. Zeit., 1890. 

Simon and Hock .Johns Hopkins Hosp. Bull., 

1890. 
Sonnenberger. . .Th. M., 1888, ii. 

Spitz Th. M., 1887. 

Spitzes Centralb. fiir Therap., 1890, 

viii. 

Umbaoh A. E. P. P., xxi. 

Verbeuil Sem. M<;d. 1891. 

Von Noorden B. K. W., 1884, 523. 

Wood, Reichert and Hare. .T. G., ii. 803. 
Yodng N. Y. M. R., 1890. 

ACETOPYR1N. 

Braun W. K. W., 1900, No. 39. 

Meitner St. P. M. W., 1900, xx. 

EUPYRINE. 

Overlach C. I. M., 1900. 

Porges W. M. Bl., 1901. 

ACETANIL1DE. 

Bokai D. M. W., Oct. 1837. 

Brown A. J. M., Dec. 1901. 

Cahn and Hepp ..Prog. M., Jan., 1887. 

Evans T. G., 1887. 

Freund D. M. W., 1888, xiv. 

Frothingham and Pratt. .A. J. M.S., 1895, ex. 



Hare T. G., 1887. 

Herczell W. M. W., 1887, p. 730. 

Hugher C. B. S. A., 1887, xvii. 

Jaffe and Hilbert. .Z. P. C, 1887-88, xii. 

Kumagawa V. A. P. A., 1888, cxiii. 

Lepine Lyons M., 1886, xlvi. 

Lepine and Aubert. .Gaz.M^d.de Strasbourg, 

1887, i. 

Marichaux D. M. W., 1889, xv. 

Pavai Vajna Centralbl. fur ges. Therap., 

1887. 

Sembritzki Th. M. 1889, iii. 

Stengel J. A. M. A., xlv. 243. 

Stengel and White. .U. P. M. B., 1903. 

Stewart J. A. M. A., 1905, xliv. 1725. 

Taylor S. L. P. C. Y., Jan. 1889. 

Weili B. G. T., cxii. 150; Thesis, 

Paris, 1887. 

ACETPHENETIDINUM. 

Crombie Pract., 1889, xliii. 

Falcone and Gioffredi. .A. I. B., xxxiv. 
Hinsberg and Kast. .Centralb. f. ges. Therap., 

April, 1887. 
Hirschfelder .. .D. A. K. M., 1888-89. xliv. 

Hollopeter M. News, 1889. 

Ledoux. Rev. de MeVi., Paris, 1892, 

xii. 
Lee Memphis Medical Monthly, 

1892, xii. 

Ott J. N. M. D., 1888, xv. 

Mahnert D. M. W., 1888, xiv. 

Muller B. K. W., 1888, 613. 

Wood, Jr., and Wood. .U. M. M., July, 1900. 

PHENOCOLL. 

Balzer Th. M., 1892. 

Hertel and Herzog. .D. M. W., 1891. 

PYRAMIDON. 

Filehne B. K. W., 1896. 

Jaffe I. B. I. M., 1902. 






CLASS II— LOCAL REMEDIES. 



FAMILY I.— STOMACHICS. 

STOMACHICS are drugs which especially affect the mucous mem- 
brane and other coats of the gastro-intestinal trad so as to increase 
functional activity. A simple bitter is a substance of vegetable origin 
ano! of a bitter taste, which has no influence upon the general system, 
but markedly affects the stomach as a stimulant. Borissow found 
that the introduction of tincture of gentian into the mouth, in con- 
junction with the presentation of food, produced a greater flow of 
gastric secretion than did the food alone. He believes that this action 
is a reflex one, depending on the bitter taste. Simple bitters probably 
influence, however, not only the peptic glands but also the muscular 
fibres, since Paul Terray found that the movements of the excised 
stomachs of dogs, kept in a warm salt solution, were increased in the 
order of naming by extract of gentian, cetrarin, condurangin, extract 
of taraxacum, quinine, and extract of quassia. Cetrarin was remarka- 
ble for its influence upon the intestinal movements. Although 
simple bitters may, by increasing the amount of food taken, affect the 
general nutrition of the body, they are essentially locally acting drugs. 
Probably all bitter vegetable substances are stimulants to the gastric 
mucous membrane, but in many of them, as in morphine and strophan- 
thin, such power is overshadowed by other inherent properties. Some 
of these active bitter vegetable substances are indeed employed on 
account of their influence upon the alimentary tract, notably quinine 
and strychnine, but in others of them, like morphine, the local is 
entirely swallowed up in the general influence. By virtue of their 
irritant action the simple bitters produce, when in overdose, nausea, 
and may even cause active irritation of the gastro-mucous membrane. 
They have also some tendency to affect the bowels. They are essen- 
tially irritant, and are contraindicated by inflammation or over- 
sensitiveness of the alimentary mucous membrane. They are especially 
indicated by loss of appetite, when such loss of appetite is the outcome 
of a depressed condition of the stomach, but when it is the result of 
gastro-inflammation they will do harm. A second class of stomachics 
are the so-called aromatics, which depend for their activity upon the 
presence of a volatile oil. They differ from the simple bitters in being 
more powerful but less permanent as local stimulants. (See page 478.) 
A third class of drugs contain both volatile oil and bitter principle, 
and unite the properties of the aromatics with those of the simple 
bitters. These are the so-called aromatic bitters. 

475 



476 LOCAL REMEDIES 

SIMPLE BITTERS. 

QUASSIA. 

Under the name Quassia the United States Pharmacopoeia recog- 
nizes the wood of the Picrasma excelsa (Jamaica quassia), a large 
tree growing in the island of Jamaica, and of the Quassia amara 
(Surinam quassia), a shrub found in Guiana and neighboring parts of 
South America. Each of these contains a bitter principle; these while 
closely allied chemically, are not regarded as identical. The precise 
chemical nature of these principles, known respectively as picrasmin 
and quassin, is not clearly understood. 

Official Preparations : 

Extractum Quassia 1 1 to 3 grains (0.06-0.2 Gm.). 

Fluidextractum Quassia? 5 to 10 minims (0.3-0.6 C.c). 

Tinctura Quassia? (20 per cent.) | to 1 fluidrachm (2-4 C.c). 

Physiological Action. — Quassia can hardly be said to be poison- 
ous to man, the largest doses producing in the adult only gastric 
irritation, but F. Venn has reported a case in which in a young child 
the injection into the rectum of a decoction representing two ounces 
of quassia was followed almost immediately by vomiting, stupor, 
relaxation, and collapse, ending in death. According to I. Hoppe, 
quassin, when given to frogs in doses of one grain, will produce weak- 
ness, convulsions, respiratory and cardiac failure, ending in death. 
Locally, quassin is a distinct irritant. In man, five milligrammes of 
the pure crystalline form notably increased the secretion of bile and 
of urine, and caused some looseness of the bowels and stimulation 
of the bladder; while fifteen milligrammes produced violent frontal 
headache, burning pains in the oesophagus and throat, nausea, 
vomiting, vertigo, excessive nervous restlessness, diarrhoea, and very 
frequent micturition, but diminished renal secretion.* 

Therapeutics. — Quassia is probably the most active of all the 
simple bitters, and may be used whenever such remedies are indicated. 
In cases of seat-worms in children, a strong infusion of quassia (two 
ounces to one pint) affords a most harmless and efficient injection. 
Its exhibition should be preceded by an enema of simple water, after 
a stool, so as thoroughly to wash out the rectum and allow access to 
every fold of the rectal mucous membrane. 

GENTIAN. 

The root of Gentiana lutea, or the yellow gentian of the Alps. 
This root occurs either in pieces of various sizes and shapes, but 
usually several inches in length, or else in transverse slices. The texture 
is spongy, the odor peculiar, and the taste bitter. It contains gentisic 
acid, which was discovered by Leconte and is tasteless and physio- 

*B. G. T., ciii. 410. 



STOMACHICS 



177 



logically inert. The active principle is probably gentiopikrin (Kro- 
mayer), a neutral, crystalline substance, of an intensely bitter taste. 
Official Preparations: 

Extractum Gentians 2 to 4 grains (0.13-0.26 Qm.). 

Fluidextractum Gentians 10 to 30 minims (().«» 2.0 C.c). 

rinotura Gentians Composita (,10 per cent .) . 1 do 1 Quidraehma ( l -l<> Co.). 

Therapeutics. -Gentian is one of the most efficient of the simple 

bitters, and may be used whenever such a remedy is indicated. The 
most largely used of its preparations is the compound tincture, which 
contains gentian, bitter orange peel, and cardamom. 

Calumba. — The root of Jateorhiza palmata, a climbing vine of 
Mozambique. It occurs in the shops in transverse disk-like slices. 
oval or circular in outline, one or two inches in diameter, of a spongy 
texture, having a yellowish surface, a very bitter taste, and a slightly 
aromatic odor. It contains a great deal of starch, besides berberinc. 
and, it is said, in lesser amount, columbin, a bitter neutral principle 
crystallizing in rhomboid prisms or needles. F. Roux has found 
that columbin given to pigeons in doses of ten centigrammes pro- 
duces death, preceded by failure of the appetite, marked signs of 
gastro-intestinal irritation, and jaundice. 

Official Preparations : 

Fluidextractum Calumba' 15 to 30 minims (1-2 C.c). 

Tincture Calumba' (10 per cent.) 1 to 2 ftuidrachms (4-8 C.c). 

Chirata, the herb and root of Swertia Chirayita, a plant growing 
in the northern part of India, is one of the best of the simple bitters, 
and is believed by some to exert a peculiar influence over the liver. 
Whenever a simple bitter is indicated, this drug may be employed, 
especially if a cholagogue action be desired. 

fluidextractum Chirata: 5 to 10 minims (0.3-0.6 C.c). 

Berk kris. — The root and berries of Berberis vulgaris of Europe 
have long been used abroad as a simple laxative tonic, and the U. S. 
Pharmacopoeia recognizes the rhizome and roots of B. Aquifolium and 
other species. These plants depend for their slight medical activity 
upon the presence of berberine (see Hydrastis) and other feeble alka- 
loids. They have been used in atonic dyspepsia, especially when 
with hepatic torpor; also as alteratives in constitutional syphilis. 

Fluidextractum Berberidis 30 minims (2 C.c). 

WILD CHERRY. 

Wild cherry bark is the product of Prunus (Cerasus) serotina or 
wild cherry tree, not of Prunus Virginiana or choke-cherry, whose 
name it bears. It occurs in pieces of various sizes, usually without 
epidermis. The color is a reddish cinnamon; the taste slightly 
astringent, bitter, and peculiar, resembling that of peach-leaves. It 



478 LOCAL REMEDIES 

contains tannic acid, bitter extractive, a nitrogenous, crystallizable, 
odorless glucoside {amygdalin) , and an albuminous principle {emulsin). 
When amygdalin in aqueous solution is brought in contact with 
emulsin, it is decomposed, forming prussic and formic acids and a 
colorless, thin, volatile oil, which, when pure, has a peculiar, agreeable 
odor and a burning taste. According to Liebig and Wohler, seventeen 
grains of amygdalin yield one of hydrocyanic acid: therefore, if 
thirty-four grains of amygdalin be mixed with sixty-six grains of an 
emulsion of sweet almonds, a two-per-cent. (by weight) solution of 
hydrocyanic acid will be formed. 
Official Preparations : 

Fluidextractum Pruni Virginianae \ to 1 fluidrachm (2-4 C.c). 

Syrupus Pruni Virginianae (15 per cent.). . . 1 to 4 fluidrachms (4-15 C.c). 

Infusum Pruni Virginianae (4 per cent.) 2 to 4 fluidounces (60-100 C.c). 

Physiological Action. — Amygdalin is physiologically inert, as 
much as sixty grains having been taken without result. Fifteen grains 
may cause death in the rabbit, but this is owing to its being converted 
into prussic acid by the emulsin in the herbage in the rabbit's stomach.* 

Therapeutics. — In wild cherry bark properly administered there 
are three active ingredients, — tannic acid, bitter extractive, and 
prussic acid. The amount of prussic acid is too small to cause percepti- 
ble effects, so that wild cherry bark is simply a feeble astringent and 
tonic. It has been very largely used in phthisis, and has been sup- 
posed not only to act as a tonic and astringent, but also to exert a 
calmative influence on the nervous system. 

Orexin. — Phenyldihydrochinazoline Hydrochlorate, or Orexce Hydrochlorate. — 
This complex derivative of quinoline occurs as colorless, odorless crystals, with 
bitter pungent taste: freely soluble in hot water. Originally brought forward by 
F. Penzolt as a true stomachic it has been variously reported upon by clinicians. 
According to the general reports, and especially to the experiments of Hofmann, it 
is practically nontoxic, two grains per pound weight not being sufficient to kill a 
rabbit, although after enormous doses free hemoglobin appears in the blood. Orexin 
hydrochlorate has, however, been entirely superseded by the orexin tannate, a 
yellowish, tasteless, odorless powder, insoluble in water but freely soluble in acid 
solutions, and consequently in the gastric juice. There seems to be little doubt but 
that orexin tannate is a valuable gastric stimulant in all those cases in which a simple 
bitter is indicated, and that it is contraindicated by gastric inflammation or hyper- 
acidity, and by gastric ulcer. It is stated, also, to be effective against the vomiting 
following the use of opium, chloroform, and other narcotics, and also in the vomiting 
of pregnancy. It is chemically incompatible with iron salts. Dose, five to twelve 
grains, one to two hours before meals. Owing to the insolubility of the salt it is 
much better to give it in powder than in tablets. 

AROMATICS. 

The aromatic oils are essentially local irritants, causing when taken 
into the mouth intense burning pain, and when confined upon the 
skin, rubefaction, blistering, and finally, if the contact be very pro- 
longed, more destructive changes. Internally, taken in very large 

* See Husemann (Die Pflanzensloffe). 



STOM VCHICS 179 

doses, the} cause burning pain in the stomach, increased activity of 
the circulation, and a Bpecies of intoxication. In sufficiently large 
quantities they are irritant narcotic poisons. When administered 
in therapeutic .loses they act almost exclusively upon the alimentary 
.■anal. As compared with thai of the simple bitters, their influence 

ore powerful and more transient. They do not permanently 

increase the digestive power, but simply increase action for the time 
being. They are employed chiefly t<> increase the immediate stimulant 
effect of hitter tonics upon the secretory digest! ve glands; as car- 
minatives, to stimulate t ho intestines to contract upon and expel 
flatus; to prevent the griping of purgatives; (<» disguise the taste <>f 
medicines, and to render nauseating drugs acceptable t<> the stomach; 
and to act as condiments and aid in the digestion of the food. 

It is probable thai aromatica directly after their ingestion affect more power- 
fully the digestive glandular apparatus than do bitter ionics, since Gottlieb has 

shown thai such substances as mustard, which are local irritants to the stomach, 
cause a very marked increase in the secretion of the pancreatic fluids. Even when 
gland had almost ceased its function, oil of mustard introduced into the stomach 
or duodenum caused active secretion in the pancreas. Quassia, taken as a type of 
the bitters, had no effect on the pancreatic activity. 

Injected into the circulation, most volatile oils lower the blood- 

-ure by depressing the heart's action, and even in comparatively 
small doses may cause immediate diastolic arrest. In this respect 
oil of cloves is one of the most powerful. Their cardiac action is 
undoubtedly direct and upon the heart itself: other muscular struct- 
ures would seem to be similarly affected, as H. Kobert has found that 
the oil of mace directly lowers muscular excitability.* 

When in concentrated form almost all of the volatile oils arc 

direct paralyzants to nerve-tissues, and seem to act especially upon 

the sensory nerve-endings; hence most of them arc local ancsthet- 

and some are used for this purpose in practical medicine. 

Most of them also possess antiseptic properties. 

Some of the tonic drugs containing a volatile oil also have in them 
a bitter principle which modifies their action. Such drugs may be 
known as aromatic bitters; as bitters they are less powerful than 
such drugs as quassia, ami are especially indicated when the stomach 
is delicate and easily nauseated. 

Inflammation of the stomach or bowels is the chief contraindication 
to the use of aromatics. Unlike the simple bitters, they are often 
very useful in diarrheca of nervous irritability or of relaxation, when 
no decided inflammation exists. 

■ in and Bruylant have studied to some extent the physiological action of the oils »/ 

,. jfinn'Ti'm. and aspic (Lavandula apnea I..) (Bull. Acad. Hon. Mid. de Bruxelles, 

midt'sJahrb., clx.xx. 123, and Cadeac and Meunier, Comvt.-Rend. Sue. Biolog., 

■ !., I ^" . In frogs they caused generally paralysis, with loss of reflex activity, 

■ being intact, and the sensory nervous apparatus being affected before the motor. 
I'pon the higher animals a similar effect was produced, except that oil of rosemary caused epilepti- 
form convulsions eppermini (Af. piperita) has been studied by S. I). Markuson Unaug. 
DU.. Halle. IS77; Schmidt's jahrb., clxxx. 122), who finds that while very small doses increase. 
larger ones decrease the blood-pressure and lower the bodily temperature. Most of the volatile 
oilfl have germicidal properties, and the oil of peppermint has been highly praised as a practical 

ng for hums, in.«nr/j. etc. (See The Medical Reporter o[ India, vi.) 



180 LOCAL REMEDIES 

Official Preparations: 

The following are the official preparations whose activity is chiefly owing to a 
volatile oil. 

Oleum Anisi 3 to 5 minims (0.2-0.3 G.C.). 

Aqua Anisi Vehicle. 

Spiritus Anisi (10 per cent.) J to 1 fluidrachm (2-4 C.c). 

Oleum Aurantii Corticis 3 to 5 minims (0.2-0.3 Co.) 

Spiritus Aurantii Compositus (Oils of Orange, 
Lemon, Coriander and Anise). 

Syrupus Aurantii Vehicle. 

Tinctura Aurantii Dulcis Vehicle. 

Elixir Aromaticum (1.2 per cent, of Com- 
pound Spirit of Orange) Vehicle. 

Elixir Adjuvans (Aromatic Elixir and Fluid- 
extract of Licorice) Vehicle. 

Fluidextractum Aurantii Amari 15 to 30 minims (1-2 C.c). 

Tinctura Cardamomi 1 to 2 fluidrachms (4-8 C.c). 

Tinctura Cardamomi Composita Vehicle. 

Oleum Caryophylli 3 to 5 minims (0.2-0.3 C.c. I. 

Eugenol — Synthetic Oil of Cloves 3 to 5 minims (0.2-0.3 C.c). 

Oleum Cinnamomi 1 to 3 minims (0.06-0.2 C.c). 

Cinnaldehydum I to 3 minims (0.06-0.2 C.c). 

Spiritus Cinnamomi (10 per cent.) 15 to 30 minims (1-2 C.c). 

Aqua Cinnamomi Vehicle. 

Tinctura Cinnamomi 1 to 2 fluidrachms (4-8 C.c). 

Oleum Fceniculi 3 to 5 minims (0.2-0.3 C.c). 

Aqua Fceniculi Vehicle. 

Oleum Gaultheria? 5 to 30 minims (0.3-2.0 C.c). 

Oleum Betula? 5 to 30 minims (0.3-2.0 C.c). 

Spiritus Gaultheria? (5 per cent.) \ to 1 fluidrachm (2—1 C.c). 

Oleum Lavandula:- Florum 3 to 5 minims (0.2-0.3 C.c). 

Spiritus Lavandula? (5 per cent.) \ to 1 fluidrachm (2-4 C.c). 

Tinctura Lavandula? Composita J to 1 fluidrachm (2—1 C.c). 

Oleum Limonis 3 to 5 minims (0.2-0.3 C.c). 

Limonis Succus \ to 1 fluidounce (15-30 C.c). 

Tinctura Limonis Corticis Vehicle. 

Oleum Mentha? Piperita? 3 to 10 minims (0.2-0.0 C.c). 

Menthol 1 to 2 grains (0.06-0.12 Gm.). 

Spiritus Mentha? Piperita? (10 per cent.) 1 to 1 fluidrachm (2-4 C.c). 

Aqua Mentha? Piperita? Vehicle. 

Oleum Mentha? Viridis 3 to 5 minims (0.2-0.3 C.c). 

Spiritus Mentha? Viridis (1.0 per cent.) A to 1 fluidrachm (2^ C.c). 

Aqua Mentha? Viridis Vehicle. 

Oleum Myristica? 5 to 10 minims (0.3-0.6 C.c). 

Oleum Pimenta? 3 to 5 minims (0.2-0.3 C.c). 

Oleum Rosmarini 3 to 5 minims (0.2-0.3 C.c). 

Oleum Sassafras 3 to 5 minims (0.2-0.3 C.c). 

Pulvis Aromaticus (Contains Cinnamon, 

Ginger, Cardamom and Nutmeg) 5 to 15 grains (0.3-1.0 Gm.). 

Fluidextractum Aromaticum (100 per cent, of 

Aromatic Powder) 5 to 15 minims (0.3-1.0 C.c). 



STOMACHICS 



IM 



Cinnamon. The I . S. Pharmacopoeia recognizes Saigon Cinna- 
mon, i he bark of an undetermined Bpeciea of I he genus Cinnamomum, 
which comes from Cochin China; it also recognizes Ceylon Cinnamon, 
the bark of the Cinnamomum seylanicum. Much of the cinnamon of 
the markets comes from China and Is known as Caasia liar!:, or 
('hints, Cinnamon. Of those harks the Ceylon is considered t hi" 
finest anil the Cassia the poorest in quality. They all contain tannic 
add ami a yellowish volatile oil which, on account of its great fragrance 
ami very pleasant taste, is largely used as an adjuvant or to disguise 
the flavor oi less agreeable drugs. Oil of cinnamon contains seventy- 
five to ninety per cent., by volume, of cinnamic aldehyde Cinnalde- 
HYDUM, l'. S. which may also be prepared synthetically. It is a 
colorless, aromatic liquid, having the same medical properties as has 
the oil itself. 

Cloves are the unexpanded flowers of Kugenia aromatica, a tree 
native to the Molucca Islands. This source, however, is practically 
exhausted and the present supply comes from cultivated trees in the 
West Indies, the islands of the Indian Ocean and other tropical regions. 
They owe their properties to an exceedingly pungent volatile oil, 
yellowish when fresh, hut becoming darker with age. The oil of 
cloves should contain not less than eighty per cent, of eugenol. This 
latter is an unsaturated phenol corresponding in its physical properties 
to the oil of cloves. Oil of cloves, besides being used as a carminative 
and an aromatic, is often employed to benumb sensitive dentine, or 
even exposed pulp, in caries of the teeth. Dropped on a piece of 
cotton and placed in the cavity, it is much used to relieve toothache 

Oil of cloves is chiefly composed of an unsaturated phenol, Eugi - 
mil, 1". S.. which is a colorless or yellowish thin liquid, having the 
odor and taste of cloves, and becoming on exposure to the air dark 
and t hick. It may be used for the same purposes as is the oil of cloves. 

■< tea, two drachms to the pint, an infusion made with boiling water, 

ften used domestically in doses of a wineglassful or more for acute 

strual suppression and as a sudorific. 

Nutmeg (Myristica) is the kernel of the ripe seed of Myristica 
fragrans, a tree growing in the Molucca Islands. The nutmeg contains 
both a fixed and a volatile oil. Mace (U. S. P. 1890) is the arillus or 
outer imperfect supernumerary coating of the seed. Both mace and 
nutmeg depend for their activity upon the volatile oil of nutmeg. 
This, when injected intravenously into the lower animals, causes loss 
of coordination, tremors, profound coma, abolition of all reflexes, 
and finally death from respiratory paralysis, its influence upon the 
circulation being comparatively feeble.* In man, one or two nutmegs 
will usually suffice to produce a dreamy, half-unconscious intoxica- 
tion, and severe or even fatal poisoning has been caused by larger 



rimenta of 11. C. Wood; also Cadeac and Meunicr (Journ. Mid. \it., Lyons, 1890). 

31 



482 LOCAL REMEDIES 

quantities. The symptoms of poisoning have been dizziness, stupor 
deepening into coma, muscular relaxation, dilated pupils, slow pulse 
and respiration, and suppression of urine, ending in death from 
respiratory paralysis.* In animals fatally poisoned fatty degeneration 
has been found (Wallace.) 

Pimenta or Allspice is the unripe berries of Pimenta officinalis, 
a tree, native in the West Indies. 

Cardamom is the fruit of Elettaria repens, which grows in the 
East Indies. It consists of tough, seemingly fibrous, generally more 
or less triangular dry and tasteless capsules, containing a number of 
small, hard, very aromatic seeds. The colorless, highly aromatic, 
volatile oil is not official. Cardamom is a very grateful aromatic, 
much less stimulating and heating than most of the other drugs of 
its class. The compound tincture is a very elegant addition to, or 
vehicle for, tonic medicines. 

Ginger (Zingiber) is the dried rhizome or root-stock of Zingiber 
officinale, growing in the East and West Indies. Green Ginger is the 
fresh rhizome. Black Ginger is the root-stock dried with the epidermis 
on; White or Jamaica Ginger is the same, deprived of its epidermis. 
The fresher ginger is the greater is its power, and by time and ex- 
posure it becomes completely inert. Its active principles are a soft, 
acrid, aromatic resin, and a yellow, volatile oil. Ginger is much 
used in domestic medicine as a stimulant carminative in colic; given 
in hot water, it is also used as a sudorific and stimulant in the pain 
due to suddenly suppressed menstruation. It is often added with 
advantage to other remedies in dyspepsia. The syrup is used only as 
a cordial drink or vehicle. 

Official Preparations : 

Oleoresina Zingiberis J to 2 minims (0.03-0.12 C.c). 

Fluidextractum Zingiberis 5 to 10 minims (0.3-0.6 C.c). 

Tinctura Zingiberis (20 per cent.) — Essence 

of Ginger J to 1 fluidrachm (2-4 C.c). 

Pepper. — Black Pepper is the unripe fruit of Piper nigrum, a 
wood}'' vine-like plant growing in the East Indies. White Pepper is 
the ripe berries stripped of their skin and dried. It is much less 
pungent than the black pepper. The active principles of black pepper 
are a soft, acrid resin, a pungent, fiery, volatile oil, and piperine. 

In 1819 Oersted discovered Piperine, which crystallizes in colorless, 
glistening, four-sided, truncated prisms, of a neutral reaction, but 
capable of combining with acids to form salts. When pure it is 
tasteless; but very commonly it has a burning taste, due to the 
presence of some of the volatile oil of pepper. The possession of very 
active antiperiodic properties has been asserted for piperine, and it 

* Fatal case, A r . Y. Med. Record, Nov. 1886. Collection of Cases, George B. Wallace, C. M. 
R. V., 362. 



STOMACHICS 183 

was for a time employed in intermittent fever; l>ut it has fallen into 
complete disuse. Pepper is very largely used as a condiment; but, 
as its taste is more hoi than annual if, it is rarely given internally in 
medicine except as an addition to simple Witters or to antiperiodics, 
generally in thr form of the oleoresin. In atonic dyspepsia t he latter 
preparation is an excellent adjuvant to tonic pills. Schiller is said 
(Fliess) to have used piperine successfully in a case of vaginismus, 
by injecting three-tenths of a grain (0.018 Gm.) hypodermically near 
the vaginal entrance. In using piperine by hypodermic injections 
it is of the utmost importance to see thai it is free from the oil of pepper. 

Official Preparations : 

Piper. 5 to 10 grains (0.3-0.6 Gm.). 

Oleoreeina Piperis i to 1 grain (0.03 O.06 Gm.). 

Piperina 3 to 5 grains (0.2-0.3 Gm.). 

Capsicum. The (J. S. Pharmacopoeia now recognizes only the 
small, less than an inch long, —very fiery fruit of Capsicum fastigia- 
tutu. the African Pepper, or Chillies. The large, bright red, conical 
or ovate, comparatively mild peppers of the market arc from C. 
annuum; they are sometimes known as West India peppers. Capsicum 
contains as its active principle an exceedingly acrid oleoresin.* 

Capsicum is a very powerful local irritant, its oleoresin when 
applied to the skin producing in a very few minutes intense pain ami 
redness, and finally destroying the cuticle. In the alimentary canal 
it ads in a similar manner: thus, moderate doses produce merely a 
pleasant feeling of warmth in the stomach, while overdoses may cause 
gastro-intestinal inflammation, with severe pain, as well as vomiting 
and purging, followed after a time by strangury and other evidences 
of genito-urinary irritation. The chief use of Cayenne Pepper is as a 
condiment ; yet it is often added with advantage to tonic pills to 
increase their immediate action on the stomach. When there is 
habitual feeble digestion, with flatulence, its free use on food may do 

id. In adynamic diseases, especially as occurring among drunkards, 
capsicum is often very useful by stimulating the stomach up to the 
point of digesting food. Locally, either as the diluted tincture in a 
gargle or applied in powder or tincture by means of a swab, it is useful 

i rere tonsillitis, especially in that accompanying scarlet fever. 

Official Preparations: 

Capsicum 1 to 3 grains (0.06-0.2 Gm.;. 

( lleoresina Capsici i to $ minim (0.01-0.03 C.c). 

Fluidextractum Capsici 1 to 3 minims (0.06-0.2 C.c). 

AROMATIC BITTERS 

Anthemis. -Chamomile. — Roman or true Chamomile, the dried 
flower heads of Anthemis nobilis, a composite of Europe, contains a 
bluish or sometimes greenish volatile oil, a bitter principle, and a 

* The name of Cnpnirin baa been applied by diffprpnt ohsprvprs to the oil. to thp resin, ami 
to their combination, but has no definite meaning 



484 LOCAL REMEDIES 

.small amount of tannin. The infusion (one ounce to a pint) is a mild 
stomachic in doses of one to two wineglassfuls. Matricaria, or 
German Chamomile, the dried flower heads of Matricaria Chamomilla. 
is much less agreeable and effective. 

Serpentaria. — The dried rhizome and roots of Aristolochia 
Serpentaria and of A. reticulata, small herbal plants of the United 
States, contain a volatile oil, a yellowish-green resin, and a bitter 
principle. It is an elegant stimulant tonic, especially useful as an 
adjuvant to more powerful bitters. 

Official Preparations : 

Tinctura Serpentarise (20 per cent.) 1 to 2 fluidrachms 4-7 C.c). 

Fluidextractum Serpentariac 20 minims (1.2 C.c). 



REFERENCES. 



STOMACHICS. Kobert... . A. E.P. P., xv. 22. 

LlEBIG and Wohler. .Ann. Chem. Pharm. 

Bartlett Chi. M. J rDec. 1885. xxii. 1. 

Borissow A. E. P. P., 1904, li. 3(13. Roux C. R. S. B., 1884, i. 33. 

Gottlieb A. E. P. P., 1894, xxxiii. 261. Terra, y Ungar. Arch. f. Med., 1892, i. 

Hoppe IX El., 1859, xi. Venn U. M. M., 1895. 






FAMILY II.— EMETICS. 



Emetics are those drugs which are employed in the practice of 
medicine for the purpose of producing emesis, or vomiting. 

Vomiting occurs under two provocations, or in two manners. 
Thus, a mental impression, or a disordered state of the blood, may 
influence the nerve-centres directly, and emesis, spoken of as (-nitric, 



M 



1 • 





Fig. 17. — Diagram to Show the Mode of Action of Emetics. 

C. — Vomiting centre. V. — Pneumogastric nerve conveying impulses from the stomach to the 
centre. M. — Motor nerve running to abdominal muscle. (For simplicity the other efferent 
nerves concerned in the act of vomiting are not represented. Some drugs as zinc sulphate and 
mustard irritate the sensory nerves in the stomach and cause vomiting reftexly. Apomorphine 
acts directly on the vomiting centre (C). Ipecac and antimony probably act in both ways. 

results; or a peripheral irritation in the stomach itself, or in some 
other organ, as in the kidneys, may induce vomiting precisely simi- 
lar in the method of its production to the more ordinary reflex 
movements; such vomiting is called reflex or excentric. 

Emetics produce their results in both of these methods. Thus, 
tartar emetic has been believed to affect the centres directly, so as to 
cause centric vomiting, while copper sulphate has been believed to 
irritate the mucous membranes of the stomach, so as to produce 
reflex vomiting. Much doubt, however, has been thrown upon the 
old views, and it is probable that most emetics have a double influence. 
Thus, the purging of arsenic or of tartar emetic is almost certainly 

485 



486 LOCAL REMEDIES 

connected with its elimination, and is probably due to a direct action 
of the circulating poison upon the intestinal mucous epithelium, 
gland-cells, and peripheral nerves. It seems a priori almost a necessity 
that the vomiting caused by these poisons is produced in the same 
way as is the purging. D'Ornellas has found that when emetine is 
injected into the veins of animals the vomiting occurs simultaneously 
with the elimination of the alkaloid from the gastric mucous mem- 
brane, and asserts that Kleimann and Simonowitsch have determined 
the same thing with antimony. Further, antimony seems to cause 
vomiting partly by acting upon the centres, partly by irritating 
the peripheral nerve. Irritant emetics are more prompt than those 
which chiefly affect the nerve-centres; they always cause less nausea 
and general systemic disturbance than do the centric emetics. 

Another evident practical fact is, that while centric emetics will 
act in whatever way they are introduced into the system, the mechani- 
cal emetics must be exhibited by the stomach. Thus, apomorphine 
may be given by hypodermic injection, but mustard must be taken 
by the mouth. Nevertheless, it is probable that most of the so-called 
"irritant emetics" act in part by being absorbed, since A. Sacher has 
found that even zinc sulphate will, when injected in proper dose into 
the blood, produce vomiting, and Brunton and West have demon- 
strated that a peptone of copper injected into a vein causes violent 
vomiting. 

A very curious property of emetics lias been pointed out by E. Harnack, who, 
as the result of an elaborate investigation, affirms as a law that all specific emetic 
substances destroy, even when in relatively small dose, the excitability of striated 
muscular fibre. Harnack seems to establish the general truth of this; but that 
it is universal law is scarcely probable, and the connection between the two proper- 
ties is very obscure. According to H. Kobert, antimony has an effect on 
muscle-fibre only when the contact is prolonged. 

In regard to the phenomena of vomiting, there are a few points to 
which it is necessary here to call attention. First of these is the fact 
that nausea always produces, or is accompanied by, muscular relaxa- 
tion. Vomiting may take place, as from mustard, without much 
relaxation; but when it is accompanied by much nausea the whole 
system is, as it were, unbent, the skin relaxed and bedewed with 
perspiration, the pulse soft and feeble, the muscular system limp and 
incapable of exertion, and the mental acts almost suspended. During 
violent vomiting the blood is driven to the head, so that the whole 
exterior of the cranium, and probably the interior also, becomes very 
much congested. The abdominal circulation is greatly affected, and 
the blood is, as it were, squeezed out of the portal vein and its tribu- 
taries. The matters rejected consist of the contents of the stomach, 
and, in repeated vomiting, also those of the duodenum. The secretion 
from the gastric mucous membrane is very much enhanced, and 
without doubt is more or less modified. Bile in ejecta is to be recog- 
nized by the green color and the bitter taste, or more infallibly by 
testing with the proper reagents. 



K MIOTICS 187 

Tin- indications for the use of emetics arc as follows: 

1. To unload the Stomach. For this purpose 1 they arc employed in 
poisoning, or when (lie stomach is oppressed by indigestible substances 
or by its own acrid, perverted secretions. The symptoms induced by 
irritating materials in the stomach are various, and sometimes it 
requires a good deal of tact or experience to recognize their cause. 
Among them may be mentioned a feeling of weight or load in the 
stomach, gastric distress, or severe cramp or spasmodic pains, with 
or without some nausea and retching. In other eases no local mani- 
festations of trouble may bo present. Thus, convulsions in children 
are very frequently the result of gastric irritation, and are at once 
relieved by emptying t he stomach. In adu'ts, apoplectiform coma may 
offer a similar history. Occasionally urticaria, or hives, and not rarely 
st- vert 1 headache, have a similar origin, and require a similar treatment. 

2. To affect the Abdominal Viscera and Circulation.— In congestions 
of the portal circulation, especially such as follow a debauch, and in 
the condition of digestive derangement known as biliousness, emetics 
are often of service. In catarrhal jaundice they may effect much good 
by causing dislodgement of the mucus plugging the ducts. They have 
been employed in cases of biliary calculi; but the chances of forcing 
out t he calculus by external violence are probably no greater than those 
of lethal rupture of the gall-bladder. 

3. To dislodge Substances from the Respiratory Passages. — For this 
purpose emetics are sometimes used when foreign bodies have found 
entrance into the larynx; but it is chiefly in membranous croup that 
the present, indication is met with. The emetics chosen for this 
purpose should be such as act with violence without producing 
much nausea or systemic disturbance: the mechanical emetics are 
therefore the best. 

4. To produce Muscular Relaxation. — The introduction of anes- 
thesia has rendered the use of emetics to meet this application almost 
obsolete. Occasionally, however, in asthmatic or other spasmodic 
affections of the respiratory organs, emetics are still employed. For 
this purpose the drugs causing much nausea are preferred. In adults, 
lobelia is the best; in children, ipecacuanha. Nauseating rather 
than emetic doses should be employed. 

Contraindications.— The chief contraindications to the use of 
emetics are the existence of congestion of the brain and of gastric 
inflammation. Advanced pregnancy, and hernia, while they do not 
positively contraindicate the use of emetics, should cause great 
caution to be practised in their employment. 

Administration. — Emetics should, as a general rule, be given in a 
full dose, so as to avoid unnecessary repetition, and should be adminis- 
tered dissolved in water or in syrup. Their action should be assisted 
by frequent and copious draughts of tepid water, which also have 
the advantage of rendering the vomiting less painful. When for any 
reason protracted nausea is desired, the doses should be small and 
repeated at short intervals. 



488 LOCAL REMEDIES 

Hyperemesis may advantageously be divided into two varieties: 
first, such as is due to overdoses of depressing centric emetics; second, 
such as arises from irritation of the stomach, as by mechanical emet- 
ics. The treatment of the first of these consists in the enforcement of 
absolute quiet in the horizontal position, the free use of opium enemata, 
the application of counter-irritants to the epigastrium, and the use 
of alcoholic stimulants. The latter should be given in hot water, and 
should not be too much diluted. We have seen raw brandy arrest at 
once the most alarming centric emesis after the failure of other methods. 
Cocaine, creosote, chloroform, or chloroform and volatile oils are 
sometimes of value in this form of hyperemesis. When excessive 
vomiting is due to some irritant substance, the stomach should be 
thoroughly washed out by large draughts of warm mucilage, opium 
given by the rectum, a mustard plaster or blister, or, often better 
still, leeches applied to the epigastrium, and no medicine at all be 
taken into the inflamed viscus. The swallowing of small pieces of 
ice is sometimes of service. If these remedies fail, the treatment of 
this form of hyperemesis soon resolves itself into that of gastritis. 

CENTRIC EMETICS 
IPECACUANHA. 

The U. S. Pharmacopoeia recognizes the Cephaelis Ipecacuanha, 
growing in Brazil, and the C. acuminata, growing in Colombia, small 
shrubs whose roots respectively constitute the Rio, Brazilian, or 
Para ipecacuanha, and the Carthagena ipecacuanha. There is at 
present no sufficient reason for believing that these plants are specific- 
ally distinct. (See U. S. Dispensatory, 19th edition.) The true 
ipecacuanha plant has been cultivated with success in the Straits 
Settlements, producing the so-called Johore ipecacuanha. The South 
American drug comes from wild plants exclusively. 

These roots are from one-eighth to one-fourth inch in diameter 
and four to eight inches long, brown or grayish in color, variously 
bent and contorted and marked on the surface with numerous promi- 
nent rings. The root itself has but very little odor but when powdered 
has a dusty, peculiar smell and in some persons excites sneezing. The 
taste is bitter, acrid and nauseous. They depend for their activity 
upon the presence of two alkaloids, emetine and cephaeline. There 
is a third alkaloid psychotrine, which is, however, almost inert. 

The ipecacuanha roots differ largely in the total percentage of the 
alkaloidal contents, hence the requirement of the U. S. Pharma- 
copoeia that they should contain at least 1.7 per cent, of aggregate 
alkaloids. It has been believed by various authorities that the Rio 
and Carthagena ipecacuanhas — because in the former emetine, in 
the latter cephaeline, predominates — are not interchangeable; but 
the reports of the large drug firms both in Europe and in this country 
indicate that the individual roots of either vary as much in the 



EMETICS 189 

proportionate percentage of emetine and cephaeline as do Ki<> and 
Carthagena ipecacuanha, and that, therefore, these two ipecacuanhas 
may be considered as therapeutically identical. Practical differences 

in their action have no! been made out by clinicians; and the belief 
of some experimentalists thai when an emetic effect is desired Cartha- 
gena is best, and when an expectoranl effect is wished Rio ipecac 
should be used, is not well founded.* lpccacuanhic acid, with which 
the alkaloids are combined, according to Kimura, is practically inert, 
although when brought in contact with the red blood-corpuscles 
outside of the body it dissolves out the hemoglobin, 

Official Preparations : 

Ipecacuanha Emotic Dose 30 grains (2 dm.). 

Pulvis Ipecacuanhas et Opii — ■ 

Dover's Powder -(10 per 

cent.) 3 to 10 grains (0.2-0.6 Cm.). 

T . i Expectorant 1 to 5 minims (0.06-0.30 C.c). 

Fluidextractum Ipecacuanhas. \ g^ 3Q minims (2 Cc) 

Tinctura Ipecacuanha) ct Opii 

(10 per cent.) 3 to 10 minims (0.2-0.6 C.c). 

Syrupus Ipecacuanha* (7 per 

cent.) 5 to 20 minims (0.3-1.2 C.c). 

Vinum Ipecacuanha (10 per 

cent.) Emetic Dose J to 1 Suidounce (15-30 C.c). 

Local Action. — Absorption and Elimination. — Locally applied, ipe- 
cacuanha is a decided irritant, manifesting its action not only upon 
mucous membranes and upon denuded surfaces, but also causing, 
when applied by inunction, an eruption of small, discrete pustules, 
with a rather large areola, followed, it may be, by large pustulation 
and even severe ulceration. Both pure emetine and cephaeline were 
found by Lowin to be very irritant, and especially so to mucous 
membranes. Ipecacuanha rapidly yields its active principles to 
absorption. They are probably eliminated by the stomach, intestines 
and kidneys, but concerning this we have no definite knowledgef. 

Physiological Action. — When given in small repeated doses to 
man, ipecacuanha produces malaise, with nausea, and perhaps an 
increase of the secretions of the salivary glands and of the mucous 
membranes of the bronchial tubes and of the stomach. In large 
amounts it causes vomiting, accompanied by only a moderate amount 
of nausea, but by a decided increase of the secretions mentioned 
above. The vomiting, even when very large amounts are taken into 
the stomach, is not likely to be severe, nor the prostration marked. 

The general physiological action of ipecacuanha is extremely 
feeble, ait hough its alkaloids are certainly very active substances. 
The difference is probably due to the fact that ipecacuanha is 

* According to the experiments of Carl Lowin emetine is only a feeble emetic, while cephat-line 
i- a very powerful emetic. On the other hand, cephaeline does not act upon the lungs at all, so 
that the emetic influence of ipecacuanha is dependent upon the presence of cephaeline, — its 
expectorant influence upon the presence of emetine. ... , 

nlinc to Maurcl (Merck's Bericht. 1901) the lethal dose of emetine on the pigeon and 
rabbit is 0.15 gramme per kilo. Maurel also states that emetine acts upon the rabbit as a local 
anesthetic. 



490 LOCAL REMEDIES 

rejected from the stomach before it can be taken in sufficient dose 
to yield poisonous amounts of its alkaloids to absorption. 

According to D'Ornellas, toxic doses of commercial emetine cause in the frog 
diminished sensibility, muscular feebleness deepening into abolition of voluntary 
movement, with at first increased and afterwards diminished activity, and finally 
death from failure of respiration; in the mammal, similar symptoms, with the 
addition usually of severe vomiting. 

Nervous System. — Respiration. — Circulation. — According to D'Or- 
nellas and Pecholier, commercial emetine exerts no influence upon 
the cerebrum, but acts powerfully upon the motor side of the spinal 
cord, — in the frog killed with it both nerve and muscle retaining their 
susceptibility to feeble galvanic currents (D'Ornellas, Pecholier and 
Foulkrod). It causes death by respiratory paralysis, which is probably 
of centric origin. 

The action of commercial emetine upon the circulation appears to be feeble, 
since Dyce Duckworth has shown that the fall of arterial pressure which the crude 
alkaloid produces does not occur until late in the poisoning. The fall is chiefly of 
cardiac origin. Lowin has found that pure emetine and pure cephaeline diminish 
the rate and strength of the contraction of the isolated frog's heart, cephaeline being 
the feebler of the two alkaloids. Psychotrine had no distinct effect. Lowin also 
found that both cephaeline and emetine paralyze the heart in warm-blooded animals. 

Pulmonic and Digestive Organs. — As emetine injected hypoder- 
mically causes vomiting, ipecacuanha must be looked upon as a 
centric emetic; but the observation of D'Ornellas, that the emetine 
produces vomiting much more slowly when thrown into the veins 
than when given by the stomach, indicates that the local irritant 
action of the drug is a factor in the production of emesis. 

The great influence of the drug upon the abdominal viscera is 
further shown by the fact, attested by Pecholier, Dyce Duckworth, 
and D'Ornellas, that in emetine-poisoning, although there is a distinct 
fall of temperature in the mouth and on the surface of the body, in 
the intestines the temperature either remains stationary or, more 
commonly, rises. Again, the changes found after death from emetine 
are almost exclusively in the lungs and digestive organs. 

Pecholier, in his earlier experiments, found great paleness of the- lungs, with 
intense hyperemia of the stomach and the upper half of the intestines, but in some 
of his later experiments the lungs were profoundly influenced. Dyce Duckworth 
especially noted intense hyperemia of the lungs, which were in some places emphy- 
sematous, but in other portions collapsed and even affected with true consolidation. 
The lesions were much less marked in the intestines than in the lungs, which 
resembled very closely those taken from the bodies of animals killed by section of 
the vagi. The pulmonic lesions were found to be most intense in the rabbit; the 
intestinal, in the dog, cat, and guinea-pig. Magendie first observed, years ago, the 
pulmonic lesions of emetine-poisoning, and D'Ornellas has likewise recorded them, but 
has also seen cases in which ischemia of the pulmonary tissue was found after death. 

It is evident that the commercial alkaloids of ipecacuanha have a 
special influence upon the intestines and the lungs, but it has been a 
mystery why this influence should vary so in power, especially in 



EMETICS 



l!M 



regard to the lungs. Carl Lowin finds that the chemically pure alka- 
loid produces almost equal influence on the gastro-intestinal mucous 
membranes; but that, while cephaeline acts violently upon the Lungs, 
after death from pure emetine no pulmonic changes are to be found. 
It would seem, therefore, that the different results obtained by earlier 
observers have depended upon the alkaloids they have used being 
really varying mixtures of the two alkaloids. 

Therapeutics. Whenever it is desired to unload the stomach or 
to act by emesis upon disease, without inducing much prostration, 
ipecacuanha is the best of the emetics. In narcotic poisoning it is 

certain than the "mineral emetics," but. as it is less actively irri- 
tant to the stomach, it can be given more freely than they can. and 
is constantly used as an adjuvant to them. It is especially useful 
m the diseases of children, never causing the serious depression which 
tartar emetic is so liable to produce. When, however, very violent 
emesis is desired, as in membranous croup, other emetics, such as 
sulphate, are to be preferred on account of the greater force of 
their action. 

In sick stomach of nervous origin, such as occurs in pregnancy, 
minute doses of ipecacuanha have so often met with success that there 
can be no doubt of their value. One drop of the wine in a teaspoonful 
of water should be given every fifteen minutes. The use of ipecacuanha 
as an expectorant will be spoken of under that heading. 

One of the most important uses of ipecacuanha is in acute dysentery, 
all forms of which have been treated with it with asserted advantage. 
Its beneficial action is most obvious in bilious dysentery and in malig- 
nant dysentery, as is indicated by the fact that its use is most common 
in tropical climates. In sthenic inflammatory dysentery it seems to 
l>e less available, although even in this it has been strongly advocated. 
In a valuable clinical paper, A. A. Woodhull brings forward strong- 
evidence of the value of the remedy not only in dysentery, but also 
in choleriform diarrhoeas. It has likewise been used with great success 
in hepatic torpor and other forms of abdominal glandular derangement. 

It probably influences not only the intestinal glands, but also the liver, since 
Pecholier affirms that in animals killed by it no hepatic glucose can he found. More- 
over great advantage from its use may often be obtained in the condition known 
M ,, In bilious dysentenj it will often produce large tarry discharges; 

•i change in the color of the stools sometimes follows its use in catarrhal jaumha 
The mechanical effect of the vomiting induced by it in these cases, however must 
not be Lost sight of; yet it does not seem to us sufficient to account for the result-;, 
especially as some observers state that the effects noted are produced even wi.cn 
little or no vomiting occurs. It has been proved by D'Ornellas and Pecholier 
that when emetine is introduced into the circulation or into the cellular tissue 

capes with the secretions of the stomach and bowels; so that the changes 
which are provoked in these organs are evidently connect ed witl. the elimination 

of the drug. . . . 

In 1890 Surgeon-Major Harris used in dysentery the ipecacuanha root. 
deprived of its emetine, with alleged excellent results. His paper has given rise 
to considerable discussion, and Surgeon-Captain Walsh, as the result of his experi- 
ments came to the contrary conclusion that the value of ipecacuanha in dysentery 



492 LOCAL REMEDIES 

depends upon its emetine, and devised a method of giving emetine in combination 
with biniodide of mercury, affirming that in this combination the drug does not 
produce vomiting. Other clinicians, however, have confirmed the statements of 
Surgeon-Major Harris. When the ipecacuanha root has been de-emetinized it fails 
to produce vomiting, or causes only very slight vomiting; and according to the 
clinical studies of Kanthack and Caddy, it has all the curative effects of ipecac- 
uanha in dysentery, and does not cause depression. The freedom from alkaloid of 
this so-called de-emetinized ipecacuanha seems to us very doubtful.* 

As a hemostatic, ipecacuanha has been recommended by Trous- 
seau, and Pecholier asserts that in hemoptysis it is a specific. f It has 
been given with asserted advantage in flooding after child-birth, and 
Carrigen asserts that it possesses oxytocic powers. 

Administration. — As an emetic, ipecacuanha is generally 
administered in powder, thirty grains (2 Gm.) being given every 
fifteen or twenty minutes until the desired effect is produced. For 
a child a year old the emetic dose is five grains (0.3 Gm.). Its action 
should be aided and hastened by large draughts of lukewarm water. 
As a nauseant the dose is from two to five grains (0.13-0.3 Gm.). 
In dysentery it is generally best to begin with a full emetic dose, or 
with ten grains (0.6 Gm.) repeated every half-hour until emesis is 
produced. Two or three hours after vomiting, fifteen drops of lauda- 
num should be exhibited, followed in twenty minutes by five to ten 
grains (0.3-0.6 Gm.) of ipecacuanha in -pill form; this should be 
repeated every two or three hours, the amount of the opium being 
lessened, and that of the ipecacuanha increased, according to circum- 
stances. The object is to have as much of the ipecacuanha retained 
as possible. Another plan is to give larger doses (twenty grains), 
repeated every two, four, or six hours, mustard being applied to the 
epigastrium and opium exhibited as before; and it is said that after 
two or three doses tolerance is established arid the drug retained. In 
India, enemata of ipecacuanha are often employed, either as a substi- 
tute for or an adjuvant to its use by the mouth. This treatment has 
recently been imitated by Chouppe and others, and in our own practice 
found to be satisfactory. It undoubtedly often succeeds in dysentery 
and choleriform and chronic diarrhosas, and the gastric symptoms are 
almost always avoided. In chronic cases the repetition of the enemata 
sometimes produces so much local irritation as to forbid their con- 
tinuance. We have been accustomed to give a scruple of the powder 
with starch and laudanum, repeated every four hours. A decoction 
of the drug is to be preferred, as probably causing less local irritation 
and being more thoroughly absorbed. To an adult, Chouppe gives 
daily two injections of a decoction, each lavement representing two 
and a half drachms of the drug. 

As a counter-irritant, ipecacuanha is rarety used in this country; 
but in England a liniment is employed composed of four parts of the 
powder to fourteen parts of olive oil. 

* See especially A. A. Woodhull (Atlanta Med. and Surg. Journ., 1875). 
t Consult Pacific Med. and Surg. Journ., 1871). 



EMETICS 193 

Emetine has been used in doses of from one-twelfth to 
one-sixth of a grain (0.005 0.01 Gm.), but it is very harsh and 
without advantage in its action. 

APOMORPHINE HYDROCHLORIDE. 
A.pO morphine, which was discovered by Malthieson ami Wright, 

is made by dehydration of morphine, usually through the action of 
Btrong hydrochloric acid, ll OCCUTS as a snow-white powder, per- 
manent when dry, hut in solution or when exposed to moisture, 
becoming green and finally almost black. There has been considerable 
discussion as to the properties of this green product ; it seems, however, 
not to he poisonous hut to lose the characteristic activity of 
apomorphine. 

Physiological Action. Local Action. — The soluble salts of apo- 
morphine, when pure, are not irritant, and when used liypodermicall y 
should not cause pain. They are absorbed with great rapidity. 
Concerning their elimination we have no definite knowledge. 

In frogs, one to five milligrammes of apomorphine cause restlessness, followed 
by an increasing sluggishness anil muscular weakness that may end in real or ap- 
parent death. In some instances there are violent convulsions, both clonic ami 
tonic in character.* Sometimes recovery occurs after both respiration and cardiac 
action have apparently ceased. 

In dogs, one to two milligrammes cause vomiting, without any other decided 
symptoms; after slightly larger amounts, the vomiting is severe, and accompanied 
by tree salivation and muscular tremblings. After very large doses, vomiting docs 
not occur, but a condition of intense restlessness, the animal jumping, running, 
bowling, and champing constantly. The slightest noise or alarm throws the animal 
into violent excitement and terror; with pupils dilated and ears drawn stiffly bach, 
he endeavors to get out of the apartment, and even to climb the wall. After still 
larger amounts (four or five grains'), to this excitement is soon added failing mus- 
cular strength, and the hind legs arc dragged l>ehind the animal in his movements. 
The respiration is exceedingly hurried, and convulsions are suddenly developed, 
the paresis and convulsions increase, so that the animal lies upon his back, kicking 
wildly into the air, and finally die:; asphyxiated. Rabbits cannot vomit, but the 
general symptoms produced by the alkaloid in them and in cats are exactly parallel 
with those just described as occurring in the dog. Very small doses (ten milli- 
grammes, Harnack) suffice to kill the rabbit. On chickens and pigeons, according 
to C. David, it acts very much as it does upon dogs; the stage of excitement is 
very marked. After death no distinct lesions are to be found, unless, as Quehl 
believes, there is habitually an excessive hyperemia of the pons Varolii. 

To the therapeutist the chief interest in apomorphine is in con- 
tion with its power of producing vomiting; but before taking this 
up we shall briefly review what is known in regard to its general 
actions. 

'Nervous ami Muscular Systems. — The action of apomorphine upon 
the cerebrum seems to be that of a primary stimulant delirifacient 
and final paralyzant. The cause of the convulsions at present cannot 
he considered as determined. According to Reichert's experiments, 

. . \ alentil Irefc. /. Exper. Path. u. /'harm., m. 309). 



494 LOCAL REMEDIES 

both the sensory and motor nerves are first stimulated and afterwards 
paralyzed.* In opposition to the experiments of Quehl, Harnack 
found that apomorphine directly affects the voluntary muscles, and 
as his experiments have been confirmed by Reichert, there can be 
no doubt that apomorphine is a muscle-poison. 

Circulation. — The reports upon the action of this drug on the cir- 
culation are somewhat discordant. It appears to be proved that the 
therapeutic dose does not affect the blood-pressure, but, contrary to 
the statements of Seibert, Max Quehl, and Bourgeois, it has been 
shown by Harnack and by Reichert that the toxic dose does lower 
the arterial pressure and is a direct paralyzant of the cut-out frog's 
heart. Reichert has shown that the mammalian heart is similarly 
affected by the drug, and the final fall of pressure must be at least 
in part of cardiac origin. Reichert states that preceding the fall of 
pressure there is a distinct rise, which is prevented by previous section 
of the cord, and is, therefore, probably due to stimulation of the 
vaso-motor centres. The pulse-rate is markedly increased by small 
and large doses of apomorphine, the maximum usually being reached 
about the time vomiting is fairly established; subsequently, in poison- 
ing, the pulse falls below normal. Reichert believes the rise to be 
due to stimulation of the accelerators, and the fall to the influence 
upon the heart- muscle. 

Respiration. — Usually the respiration-rate is increased by decided 
or toxic doses. During the convulsive period of the poisoning the 
respirations become irregular and unequal, and they finally grow 
more and more shallow and infrequent, until death results from a 
paralysis of the respiratory centres. Both Harnach and Reichert 
have noted that in the rabbit previous section of the par vagum does 
not prevent, but rather increases, the respiratory acceleration; 
Reichert affirms that in the cat and dog no increase of the respiration- 
rate occurs under the action of the drug if the pneumogastrics have 
been cut. 

Temperature. — The action of apomorphine upon the temperature 
appears to be very trifling and inconstant. According to Ziolkowski, 
the bodily heat usually falls after large doses from 0.1° to 0.5° C. 
Moerz noticed in one man that the temperature rose during the vomit- 
ing 0.2°; while Bourgeois affirms that in man the drug has no influence 
over the temperature, and Reichert has seen in animals a rise follow 
the hypodermic but not the intravenous injection of the alkaloid. 

Emesis. — Gee was the first to announce that apomorphine is a 
certain and prompt emetic, producing but little nausea, and having 
the great advantage of acting in very small dose, a tenth of a grain 
being sufficient, when injected under the skin, to cause vomiting in 
ten minutes. The time required for action depends largely upon the 

* The only one who has carefully studied them is Reichert, and his published account is self- 
contradictory. He reasons that the convulsions are chiefly spinal, and yet says that in mammals, 
after section of the spinal cord, except "in very exceptional cases," they are confined to the anterior 
part of the body. 



EMETICS 195 

amount of the drug exhibited. After very small doses twenty minutes 
may elapse; and in Bourgeois's experiments 0.46 grain produced 

violent vomiting in less than two minutes. Alter these large dOBOS 
the emesis usually recurs once or twice at intervals of a quarter to 
half an hour. The vomiting seems to be of centric origin, as Reichert 
has succeeded in producing it when the thoracic aorta was tied so as 
to prevent any of the poison from reaching the stomach. 

Therapeutics. — Apomorphine is a safe and reliable emetic, and 
may be used whenever it is desired simply to empty the stomach. 
Apomorphine has a tendency in bronchitis to cause free secretion, 
and is especially useful in the suffocative catarrh of infants, when an 
emetic is required to get rid of the bronchial exudation. Under these 
circumstances it is said not only to act efficiently as an emetic, but 
also to render the mucus more copious and fluid. In the "drunk 
wards" of some of the Philadelphia hospitals for the relief of acute 
debauch apomorphine is preferred because the subjects habitually 
go to sleep directly after the vomiting ceases. Tull has found it 
useful in acute chorea. 

Probably because it has morphine in its name there was at one 
time a rather wide-spread belief that apomorphine was not a suitable 
emetic in narcotic poisoning. In fact, however, narcotics influence 
the action of apomorphine only as they do that of every other emetic, 
and if apomorphine has any narcotic influence it does not interfere 
with its emetic action. Apomorphine may, therefore, be used in any 
poisoning: hypodermically given, it is often especially useful as a 
reinforcement of a mechanical emetic exhibited by the mouth. 

Administration. — As an emetic, apomorphine has usually been 
administered hypodermically, in doses of one-tenth of a grain (0.006 
Gm.), repeated every ten minutes until some effect is induced; but 
it may be exhibited by the stomach in double the amount. In cases 
of severe poisoning, where time is of great moment, it may be well to 
give as much as one-fourth of a grain (0.016 Gm.) at a single injection. 
In feeble persons, however, caution must always be exercised in 
using it, as one-fifteenth of a grain has caused death in seven minutes 
in an adult, fifty-four years old, suffering from chronic bronchitis with 
marked emphysema. * The expectorant dose is one-sixteenth of a 
grain (0.004 Gm.). Care must be exercised in its use in children. 
Loeb gave hypodermically 0.03 grain to an infant, thirteen months 
old, suffering from capillary bronchitis: the free vomiting which was 
induced left the infant much exhausted. In a very few cases apo- 
morphine has failed to vomit, and even caused startling symptoms: 
so that care should be exercised not to push the remedy too far. 
Carville affirms that three-tenths of a grain has caused a syncopal 
condition in an adult, and Prevost details a case in which syncope 
and threatening collapse were apparently induced by a very small 
dose. In children especially must care be exercised, since, according 

N. V. M. K., 1S77. 6B4. 



496 



LOCAL REMEDIES 



to Harnack, the drug is very liable to produce collapse. Greenish 
preparations of apo morphine should not be used unless the dose be 
very small. Constantine Paul states that if glycerin be used as the 
sole menstruum the solution will keep three or four days. Carvillc 
affirms that glucose acts well as a preservative, and it is also asserted 
that a few drops of muriatic acid will suffice. 

Mechanical or Reflex Emetics. — The only drugs of practi- 
cal value in this group are ground mustard and zinc sulphate; 
copper sulphate being so irritant as to be dangerous, and alum and 
other drugs sometimes used too uncertain in their influence. 

Mustard flour is very prompt and even violent in its action, and 
is to be used when it is desired simply to evacuate the stomach rapidly. 
As it is generally to be had at once, it is especially useful in such 
emergencies as narcotic poisoning. Dose, a heaped tablespoonful in 
half a pint of water, repeated, if necessary, in ten minutes. 

Zinc sulphate is a very sure emetic, much used in narcotic poison- 
ing, especially with ipecacuanha or apomorphine. Dose, thirty grains 
(2 Gm.) dissolved in about two ounces of water: it may be repeated 
in fifteen minutes, if necessary. 



REFERENCES. 



EMETICS. 



Bourgeois. 



Carrigen. . . . 
Carville. . . . 

Chouppe 

David 

D'Ornellas. 
Foulkrod. . . 
Gee 



Harnack 

Harnack 

Harris 

Kanthack and 
Kimura 



. . . De l'Apomorphine, Paris, 

1872. 
. ..N. Y. M. J., 1878. 491. 
...G. H. M. C, 1874, 408. 
. ..B. G. T., June, 1874. 
. . .Gaz. Med. 1874, 465. 
...Gaz. He'd., 1873. 537. 
.. ,P. M. T., viii. 554. 
. . .St. Bartholomew Hosp. Rep. 

v. 215. 
. . .A. E. P. P., iii. 44. 
. ..A. E. P. P., ii. 291. 
. . . L. L., 1890, ii. 
Caddy. .Pract., 1893. 
...A. I. P., 1903, xi. 



Robert A. E. P. P., xv. 36. 

Loeb S. Jb., civ. 272. 

Lowin A. I. P., 1902. 

Matthieson and Wright. Proc. Royal Soc, 

xvii. 455. 

Pecholier B. G. T., xcvii. 49. 

Pecholier Gaz. Mexl.. 1862. 

Prevost L. M. R., 1875, 183. 

Quehl In. Dis., Halle, 1872. 

Reichert P. M. T., x. 110. 

Sacher Thesis, Dorpat, 1893. 

Seibert L. M. R., i. 44. 

Tull N. Y. M. J., March 11, 1905. 

Woodhull Atlanta Med. Surg. Journ., 

1875. 

Walsh Indian Med. Gaz., 1891. 

Ziolkowski In. Dis., Greifswald, 1872. 



FAMILY III.— CATHARTICS. 



The question whether the cathartics cause movement of the bowels 
by increasing the intestinal secretions or the peristaltic activity 
has been much discussed. 

The methods which have heen most used for investigating the 
action of drugs upon the intestinal secretions are those of Thiry and 
of Moreau. Thiry's method consists in drawing out a knuckle of 
intestine and making a fistulous opening through the skin, closing 




B 

Fig. 18 — Morkau's Experiment. 

Three loops of intestine are tied off. Into B is injected the cathartic and the intestine 
returned to the abdomen. After a time loop B is found to be distended with fluid while A 
and C are not. 

the other end of the piece of intestine and uniting the ends of the 
main portion of the intestine so as to reform a continuous tube, 
leaving a cul de sac, which can be studied through the fistulous opening. 
The method of Moreau consists in tying off a loop of the intestine 
into three portions, in the central one of which the tract is injected 
and its fluid content compared with the ligated piece on either side 
which are taken to indicate the normal secretory rate of intestinal 
fluid. To determine the muscular activity of the intestines peristaltic 
movements may be directly observed, the animal being immersed in a 
warm physiological salt solution ; or the rate of passage of fecal matter 
or foreign body may be observed; or an inflated rubber balloon may 
he inserted into the intestines communicating with a Marey tam- 
bour and the compression of the balloon being taken as an index of 
peristaltic activity. 

The results which have been achieved by these methods of study 
are so absolutely contradictory as to make direct conclusions con- 
32 497 



498 LOCAL REMEDIES 

cerning the mode of action of cathartics almost impossible. The 
causes of this confusion in results we believe are three. In the first 
place, a large number of observers have considered that all cathartics 
act in the same manner. It seems to us absurd to take it for granted 
that substances differing so widely in their chemical composition, in 
their general physiological effects, and the clinical results from their 
use, as sodium sulphate, aloes and croton oil act in the same manner 
on the intestines. The second reason of failure is the variance from 
natural conditions in many of the methods of experimentation. 
Finally it must be remembered that the alimentary tract of both 
dog and rabbit are functionally very different from the human 
intestinal canal. 

As we believe that the vegetable cathartics act differently from 
the salines we deem it wiser to consider their actions separately under 
their respective heads rather than to go into a detailed description 
of the confusing results which have been obtained with the cathartics 
in general.* 

The indications to fulfil which cathartics are used, are as follows: 
1. To unload the Bowels. — It is not necessary, in a work like the 
present, to say anything about the evil results of retained fecal matter, 
but only to point out the methods of relief. Before this can be done 
to advantage, however, a summary of the causes of constipation is 
required. Constipation may be well divided into acute and chronic. 
Acute or temporary constipation is that which occurs under special, 
transient circumstances, as in convalescence from acute disease, and 
in pregnancy. It is to be relieved by the use of laxative articles of 
diet, and, this not sufficing, by laxatives or purgative medicines. It 
should never be forgotten that acute constipation is sometimes due 
to organic affections of the alimentary canal, such as enteritis or 
intussusception, or is caused by mechanical obstacles, such as a 
hard foreign body or an enormous gall-stone. It is evident that such 
cases are not simple constipation, — that the treatment required is 
essentially different from that of the latter affection, and is various 
according to the lesion. For the diagnosis and treatment of these 
diseases the reader is referred to works on the practice of medicine. 
Chronic constipation may be due to sedentary habits of life; to habitual 
overwork, especially of the nervous system; to a deficiency of intestinal 
secretion and of peristalsis, apparently natural to the individual and 
without obvious cause; to long-continued voluntary habit of restrain- 
ing the desire to go to stool; to lead or other forms of poisoning; and 
to diseases of the nervous system producing a paralytic state of the 
intestinal muscular fibres. It is evident that in the treatment of these 
various forms of constipation due regard must be paid to the cause, 
which should always, if possible, be removed. There are also certain 
cardinal principles which apply to the treatment of all forms of 
chronic constipation. They are as follows: 

* For a consideration of the effects of drugs upon the biliary secretion see page 514. 



CATHARTICS 199 

\ voluntary effort at defecation is to be daily made at a fixed hour, 
whether the desire exists or not. 

Medicines are to be avoided as far as possible, a sustained effort 
being made to regulate the bowels by means of diet. 

In very many cases the daily use of eneinata of cold water, with 
attention to diet, suffices to attain the desired result. 

If medicines become necessary, as small an amount as will suffice, 
and the mildest drugs, are to be used. Purgatives or laxatives are 
at best merely temporary devices, and if abused in costiveness increase 

the trouble. So far as call he. the attempt should he to produce a 

permanent impression, an alteration of the intestinal glandular action 
or peristalsis. Tims, when atony of the muscular coat exists, strych- 
nine, or, according to comparatively recent experiments and clinical 
observations, physostigma may he employed; if the hepatic or 
other glands are habitually torpid, nitro-hydrochloric acid maybe 
administered. 

When constipation is attended by low spirits and a coated tongue, 
it is almost always due to a deficiency of secretion, and may be looked 
upon as a form of dyspepsia: in such cases nitro-hydrochloric acid is 
especially valuable, but sometimes a mild mercurial course seems 
almost imperative. 

A second use of cathartics under the present indication is to remove 
offending materials, as indigestible or irritant food, foreign bodies, 
acrid discharges, etc. In many cases of indigestion with undue fer- 
mentation in the alimentary canal a brisk cathartic does great good 
by producing the expulsion of micro-organisms. The possible im- 
portance of this is shown by the experiments of Gilbert and Dominici. 
who found that a single dose of a saline caused in a healthy man the 
expulsion of over four hundred and eleven billion organisms. 

2. To deplete. — On account of the large serous flow which they 
produce, the hydragogue cathartics when freely exhibited cause a 
very decided general depletion. 

Local depletion by means of cathartics is called for in congestion of 
the portal circulation, as well as in di/sentery and other acute intestinal 
inflammations. Under the first of these conditions may, we think, 
be included without violence cases of so-called torpidity of the liver, 
which will be discussed in the article upon mercurials (p. 513). In 
acute intestinal inflammations the salines are to be preferred when 
depletion is desired, as they produce large serous discharges and are 
not irritant. 

:$. To promote Absorption. — By emptying the blood-vessels the 
cathartics favor the absorption of t ho exuded fluid in general dropsy. 
For this purpose the hydragogues, and especially elaterin, are the 
best purgatives. The production of catharsis is the surest method 
of relief in general dropsy, also in ascites; in other forms of local 
effusion its effects are less marked. As, however, purgation is 
the most exhausting of all the plans employed for the cure of 
dropsy, due regard must always be had to the strength of the 



500 LOCAL REMEDIES 

patient. It is frequently necessary actively to support or even to 
stimulate while it is being carried out. 

4. To revulse. — The long tract of the alimentary canal affords a 
great extent of surface upon which to practise revulsion in certain 
brain diseases, as in mania and rheumatic or gouty irritation of the 
cerebrum. In hyperemia of the brain, purgatives do good by depleting 
as well as by acting as revulsives. The drastics should be preferred. 

5. To eliminate. — It cannot be doubted that the use of purgatives 
in such diseases as fevers and cholera, with the idea of eliminating 
some materies morbi, rests simply upon a crude, unproved, and proba- 
bly false pathology. In rheumatic disease and in gout it is more prob- 
able that they do good in this way, although it is by no means certain 
that the advantage derived from their use is not simply due to 
depletion. In cases of retained renal secretion, the evidence is very 
decided that they do aid in expelling the products of retrograde 
metamorphosis. 

Enemata. — When it is desired simply to unload the lower bowels, 
the object can often advantageously be attained by injecting various 
materials into the rectum, so as, by mechanical distention or by 
irritating the mucous membrane, to stimulate the peristaltic action. 
The simplest, least irritant, and least active enema is one of cold 
water. In cases of habitual constipation, especially when complicated 
with piles, the injection of a pint of cold water at a fixed hour daily 
often acts most kindly. The ordinary "opening injection" consists of 
a pint of water and a tablespoonful, each, of salt, molasses, and soft 
soap; castor oil is often added to it, and, if it be desired to make 
it very active, a teaspoonful of oil of turpentine. 

Large Enemata. — Except in individuals of extreme nervous irrita- 
bility, there is little difficulty in filling the large intestine with water, 
and sometimes the fluid can even be made to enter the small intestine. 
The greatest gentleness should always be practised, a forcing syringe 
never being used. The apparatus should consist of a rectal tube, and 
an ordinary india-rubber tube, four feet long, fitted to the rectal 
tube and to a funnel, india-rubber bag, or other receptacle. The 
patient should lie upon his back with the hips elevated, or in the 
knee-chest position, so that the pelvis may be much higher than 
the shoulder. The rectal tube having been introduced into the rectum, 
the end with the receptacle containing water is to be raised vertically. 
It is essential that the tube be fitted with a cock, or be pinched, so 
as to regulate the passage of the liquid. In this way from five to nine 
pints are readily injected. Unless it is especially desired to get the 
effect of cold or heat upon the intestine, the water in the receptacle 
should be about 100° F. 

Large enemata are especially valuable as affording a means of 
locally treating the intestines. Very frequently in dyspepsia, chronic 
constipation, and other functional diseases of the digestive organs, the 
large intestine habitually contains scybala, fecal matters, acrid 
secretion, or other irritant substances, whose removal two or three 



CATHARTICS 50] 

times a week by means of simple water or water impregnated with 
half a drachm of sodium bicarbonate to the quart brings great relief. 
In dysentery, chronic or acute, and iii pseudo-membranous colitis or 

■lis. by means of t lie large enemata, local application can be made 

to the colonic mucous membrane. In this way, in acute dysentery, 
water, antiseptics, germicides, bismuth subnitrate, and other appro- 
priate remedies can be used. In chronic dysentery, one drachm of 
silver nitrate dissolved in half a gallon of water is often of the greatest 
ser\ ice. 

\& originally recommended by Mosler, these injections are some- 
times very useful against intestinal parasites. In this way especially 
may they be used against the oxyuris vermicularis, which often inhabits 
the whole of the large intestine. In had cases of seat-worm, the large 
injection should always be employed. In obstinate cases of tape- 
worm, when the worm has been weakened, and partially or completely 
expelled from the small intestine under the influence of vermi- 
cides given by the mouth, filling the colon with a medicated solution 
often brings success. Sometimes a saturated solution of salt suffices, 
or quassia may be employed. Mosler records as especially effective a 
tablespoonful of chlorine water to every pint and a half of water. 
A. Rohrig having found that intestinal injections of water have a 
very great influence over the secretion of bile, Mosler has been led to 
try forced enemata in catarrhal and other jaundices, with asserted 
good results. 

Hypodermic Purgation. — Although several substances are capable 
of producing purgation when injected hypodermically, Apocodeine is 
the only known substance which appears to have practical value. 
It seems to be moderately effective, producing soft but not numerous 
or very watery stools: it is probably not effective when the constipa- 
tion is obstinate, and not sufficiently drastic or hydragogue in its action 
to be of value in cases of severe diseases of the brain when counter- 
irritation through the intestinal tract may be desired. From one- 
t bird to one grain (0.02-0.06 Gm.) of the hydrochlorate may be injected 
with proper antiseptic precaution. 

According to W. E. Dixon, podophyllo-toxin given hypodermically purges 
actively, but produces severe local inflammation and sloughing at the point of 
injection. Apparently the first to notice that apocodeine had the power of increas- 
ing intestinal peristalsis was Guinard. After him, Toy determined that when it was 
given by the mouth or hypodermically it acted as a laxative; and Raviart and 
Berth) in a numl>er of cases found the injection of thirty minims (2 C.c.) of a one- 
per-cent. watery solution of apocodeine hydrochlorate produced soft stools without 
any other disturbances except some pain and diffused redness at the place of injec- 
tion. W. E. Dixon determined by experiments upon the lower animals that apoco- 
deine lessens blood-pressure by dilatation of the blood-vessels and increases intestinal 
peristaltic action. Heinze has used the remedy in a large number of cases. He 
finds the dose of 2 C.c. of a one-per-cent. solution is usually insufficient, and that 
the strength of the injection may be increased to two or even three per cent.; and 
in the latter dose is almost certainly effective, in some cases the effect continuing 
several days. No narcotic influence was perceptible, but in a number of cases 
there was distinct irritation at the place of injection. 



502 LOCAL REMEDIES 

Fronmuller says that one to three grains of Merck's aloin dissolved in hot water, 
administered hypodermically, act as an efficient purge; R. Kohn states that in 
his hands aloin of three different commercial varieties, hypodermically administered 
in ten times the dose employed by Fronmuller, failed to act. In 1881, as the result 
of an elaborate investigation, A. Hiller reached the conclusion that while there 
are four purgatives, — namely, aloin, cathartic acid, and the pure colocynthin and 
citrullin of Merck, — which are capable of purging when given hypodermically, 
they are all too irritant for practical use; a conclusion w : hich was confirmed by 
Koldstock. According to Meyer, the irritant action of Barbados aloin is largely 
due to the precipitation in the subcutaneous tissue of insoluble and extremely 
irritating crystals of the drug, and may to a considerable extent be overcome by 
the use of formamide as a veliicle. 

Laxative Foods. — As has been already stated, constipation should 
always, when possible, be overcome by laxative food. There are 
two qualities by virtue of which food is laxative. Chief of these is 
bulk. All aliment which contains a large amount of innutritious 
material affords a large residuum, which, by distending the intestine, 
stimulates peristalsis. Contrariwise, articles of diet which are highly 
nutritious and afford but little residuum are constipating. This 
holds good, more or less strictly, among the lower animals. Thus, 
the flesh-eating carnivora are habitually constipated, the grass-eating 
herbivora very generally lax. 

Owing to its containing so little of the innutritious portion of the grain, the 
finest white flour favors a costive habit, while the "cracked wheat," in which the 
whole grain is eaten, is laxative, — as to a still greater degree is bran, which is com- 
posed almost wholly of the husk of the wheat, the least nutritious portion of it, 
and therefore leaves a large residuum after digestion. Cracked wheat is boiled into 
a sort of jelly-like mass, and eaten with cream and sugar, while bran is taken in the 
form of bran bread, bran crackers, or bran mush. Unbolted flour, containing the 
whole of the grain, is about equal to cracked wheat, and is often made into bread. 
Indian meal, in the form of cakes or of mush, is highly nutritious and somewhat 
laxative; oatmeal is decidedly laxative, scarcely so much so as bran, but much 
more nutritious. When it agrees with the stomach, and is digested, it is prob- 
ably the best of all these laxative articles of food. As the oats produced in 
southern climates are very inferior, care should be taken to procure oatmeal man- 
ufactured from Northern grain. It should be thoroughly cooked, and is best eaten in 
the form of a thick porridge. In dyspepsia all of these articles sometimes disagree 
with the stomach and cannot be used. 

Some dietary articles seemingly possess dynamic laxative powers, — 
i.e., they exert a direct action which is not mechanical, but is similar 
to, although far less active than, that of the true purgatives. They 1 
intensify the intestinal action. Chief among substances of this class 
are molasses (Syrupus Fusctjs) and its congener, brown sugar; white 
sugar (Sacchartjm, U. S.) probably does not share these laxative 
powers; sugar of milk (Sacchartjm Lactis, U. S.) is probably also 
nearly inert. Of course, great care is usually necessary in taking 
advantage of the laxative virtue of molasses, on account of the danger / 
of producing fermentation and acidity in the prima? via?. J * 

/ There are certain foods which combine the two methods of action/**" 
spoken of, chief among which are fresh acidulous fruits, such as^~ 
apples, pears, etc., and dried fruits. Of the latter several are recog- 



CATHARTICS 



503 



1 l>y the Pharmacopoeia, including the fty (picus), the prum 

(PKUNUM), and t he tamarind (TAMARINDTJS), and the pulp of the 

ia fistula. Besides these should l>e mentioned as containing sim- 
ilar properties, manna, which is the exudation of the European ash, 
Fraxinus ornus, and contains a saccharine principle, mannite, to which 
apparently it owes its laxative properties as well as its sweet taste. 

Among constipating articles of diet, it is only necessary to call 
attention to milk as one of the most decided of the class. 

The purgatives have frequently been divided, according to the 
severity of their effects, into laxatives, purgatives and drastics. As 
the difference, however, is frequently a question of dosage and takes 
no cognizance of certain marked pharmacological relations, the follow- 
ing division appears to us to be more scientific and at least equally 
as valuable from a clinical standpoint: 

Purgatives containing derivatives of anthraquinone, — rhubarb, 
senna, cascara sagrada, frangula, and aloes. 

Vegetable cathartics containing resinous glucosides and acids, — this 
includes most of the so-called drastics, as jalap, podophyllin, colocynth, 
Bcammony, and gamboge; also the more mildly acting euonymus. 
ithartic oils, — castor oil, croton oil. 

Salines, — the salts of sulphuric, phosphoric, citric and tartaric acids. 

Mi rcurials. 

FIRST GROUP. 

A number of vegetable laxatives contain derivatives of anthra- 
quinone [C u H 8 0,] to which they owe, at least in part, their laxa- 
tive properties. Among these principles the most important, which 
have so far been isolated, are emodin — trioxymethyl-anthraquinone 
[C ll H 4 (CH 3 )(OH) 3 0._ > ] and chrysophanic acid, dioxymethyl -anthra- 
quinone [C u H 5 (CH :! ")(OH) 2 2 ]. The most prominent plants containing 
anthraquinone derivatives are rhubarb, senna, aloes, cascara sagrada 
and frangula. It is to be noted, however, that these plants appear 
to contain other bodies which aid their aperient properties, and that 
the pure principles are frequently less purgative than crude drugs, 
perhaps for purely physical reasons. 

The anthraquinone derivatives seem to cause catharsis by a direct 
irritant influence upon the intestine, leading, thereby, to some increase 
in the fluid constituents of the bowel, but chiefly hastening peristalsis. 
This irritation, it should be noted, is never severe enough, even after 
large doses, to give rise to serious inflammation such as may be caused 
by the drastics. It does, however, contraindicate the use of this 
group as purgatives in cases of enteritis. 

RHUBARB. 

The dried rhizome of Rheum officinale, Baillon, and other species 
of Rheum growing in China, and Thibet. 

The rhubarbs are large perennial herbs with leaves two to four feet 
long; the leaves of one species being used in this country as a food stuff. 



504 LOCAL REMEDIES 

Rhubarb occurs in hard, irregularly cylindrical or roundish bits, 
of a brownish-yellow color, with a pleasant aromatic odor and a 
peculiar bitter taste, imparting to the teeth a sense of grittiness due 
to the presence of a number of minute crystals of calcium oxalate. 

It contains besides emodin, a glucoside, chrysophan, which yields 
on decomposition chrysophanic acid. There is also present a notable 
proportion of tannin. 

Official Preparations : 

Extractum Rhei 5 to 10 grains (0.3-0.6 Gm.). 

Pilulae Rhei Compositse (Each 2 grains Rhubarb and li grains Aloes). 
Pulvis Rhei Compositus (Rhubarb 25 per 

cent., with Magnesium Oxide and Ginger). . i to 1 drachm (2-4 Gin.). 

Fluidextractum Rhei 15 to 30 minims (1-2 C.c). 

Tinctura Rhei (20 per cent.) 1 to 2 fiuidrachms (4-8 C.c). 

Tinctura Rhei Aromatica (20 per cent.) 1 to 2 fiuidrachms (4—8 C.c). 

Mistura Rhei et Sodae (li per cent.) J to 1 fluidounce (5-30 C.c). 

Syrupus Rhei (10 per cent.) 2 fiuidrachms (8 C.c). 

Syrupus Rhei Aromaticus (3 per cent.) 4 fiuidrachms (15 C.c). 

Physiological Action. — Rhubarb is somewhat stomachic, tonic, 
actively purgative, and, owing to its tannic acid, secondarily astrin- 
gent, leaving a decided tendency to constipation after the primary 
purgation. Owing probably to its chrysophanic acid, it gives a yellow- 
ish color to the milk of nursing women and to the urine. Rhubarb 
urine is to be distinguished from that of jaundice by its becoming 
purplish-red on the addition of an alkali. 

Therapeutics. — Notwithstanding its astringent property, rhubarb 
is largely used as an habitual laxative, because it does not impair, 
but, on the contrary, seems to strengthen, the appetite and the diges- 
tion. It should not be used in a high sthenic state of the system, or 
when depletion is necessary, but is very valuable when it is desired 
simply to unload the bowels in a debilitated subject. It is much 
used in diarrhcea, with intestinal weakness or relaxation, to unload 
the bowels of acrid secretions. The aromatic syrup combined with an 
alkali is especially serviceable in the summer bowel-complaints of 
children when the stools are greenish and mucous. 

ALOES. 

Aloes appears to have been produced in the Island of Socotra, 
as far back as the time of Alexander the Great, 333 B. C; and the 
U. S. Pharmacopoeia of 1890 recognized Socotrine and Barbados 
aloes, besides which a variety of aloes produced at the Cape of Good 
HojDe, Cape aloes, largely occurred in commerce. At present, under 
the general name of Aloe, the Pharmacopoeia recognizes simply aloes, 
allowing the pharmacist to use any form of aloes which conforms to 
the standard given in the text of the Pharmacopoeia. Aloes is not 
now produced at Barbados, while the Socotrine aloes occurs in the 
American market only in small quantities, the mass of the commercial 
drug being produced in the Island of Curacoa. 



CATHARTICS 



505 



Aloes is obtained by cutting off (he. thick, succulent leaves of 
various species of the genus aloe, allowing the juice to drain into 
skins, troughs, or other vessels, and afterwards inspissating either by 

exposure to the sun or by means of artificial heat. The aloes are 
blackish-brown or yellowish-brown, of a bitter, nauseous taste, often 
with a smooth fracture, and in the best varieties with garnetty edges; 
they yield their virtues to alcohol, imperfectly to water, and very 
imperfectly to alkaline solutions. 

T. and II. Smith in 1850 discovered in Barbados aloes a crystalline 
principle, aloin. which was shortly afterwards found by I'ereira 
to exist already crystallized in the sap of various species of aloe-plants, 
and was subsequently obtained by droves from Socotrine aloes. Aloin 
crystallizes from its aqueous solution in sulphur-yellow granules, from 
a hot alcoholic solution in star-like groups of needles. It is neutral, 
almost odorless, of a taste at first sweetish, afterwards intensely 
bitter; is soluble with difficulty in cold water, freely in boiling water 
and in alcohol. There are three varieties of aloin, — barbaloin, socaloin, 
and nataloin, obtained respectively from the Barbados, the Socotrine, 
and the Cape aloes. Aloinum, U. S., is the aloin derived from Barba- 
dos aloes or from Socotra or Zanzibar aloes. The aloin of commerce 
is chiefly barbaloin, and is certainly an active cathartic in doses of 
half a grain to a grain (0.03-0.06 Gm.). 

II. Meyer finds that the Barbados and Curacoa aloin act both on man and 
on many lower animals as a purgative, while the Natal aloin fails ordinarily to 
affect man, although it is a certain cathartic in dogs and cats. The time required 
for the Barbados aloin to produce purgation was from eight to thirty hours, which 
Meyer believes to l>e due to the fact that its physiological action depends upon its 
undergoing chemical change in the intestines. In order to facilitate this change he 
exhibited with it potassium carbonate and ferrous sulphate, and found that these 
salts markedly hastened the effect. He also found that Natal aloin, when given to 
persons who had been fed for six days an exclusively animal diet, acted as a cath- 
artic* In the lower animals Kohn found the hypodermic injections of aloin to 
cause gastro-enteritis with albuminous urine, and a peculiar inflammation of the 
kidneys; 0.1 gramme of Merck's aloin for every kilogramme of bodily weight was a 
fatal dose for the dog. Brandenburg has experimentally shown that very large doses 
of aloin cause in the rabbit a fatal necrosis of the renal epithelium; small doses 
produce a parenchymatous nephritis. 

Official Preparations: 

Aloe Purificata 4 to 10 grains (0.3-O.G Gm.). 

Aloinum J to J grain (0.01-0.03 Gm.). 

Extractum Aloes 1 to 3 grains (0.06-0.2 Gm.). 

Pilula; Aloes (2 grains) 2 to 4 pills. 

Piluls Aloes et Ferri (1 grain) 2 to 4 pills. 

Pilulffi Aloes et Myrrb.se (2 grains) 2 to 4 pilLs. 

Pilulffi Aloes el Mastiches [ Lady Webster 

Pill J(2 grains). (2 to 4 pills). 

Piluls Laxativao Composite — [A. B. S. Pills] 

(aloin 4. grain) 1 to 2 pills. 

Tinctura Aloes (10 per cent.) 1 to 3 fluidrachms (4-12 C.C.). 

Tinetura Aloes et Myrrhae (10 per cent.). ... 1 to 3 fluidrachms (4-12 C.c). 

* Consult Trans. Brit. Pharm. Soc, 1872; Brit. Med. Journ., 1887, i. 747; Bull. Thirap., xci. 
2o9, I.ond. Med. Record, 1877, 459; and Edin. Med. Journ., xx. 1002. 



506 LOCAL REMEDIES 

Physiological Action — Aloes is a stomachic, stimulant cathartic, 
remarkable for the slowness of its action. It has been supposed to 
influence chiefly, if not solely, the large intestine, and the clinical 
evidence is very strong that in overdoses it produces irritation of the 
rectum. The belief, formerly universal, that it is capable of producing 
hemorrhoids, and the statements that its habitual use in large doses 
causes tenesmus, a feeling of weight, heat, and uneasiness in the 
pelvis, and occasionally excitation of the sexual organs, are of very 
doubtful correctness. Aloin has been detected in the urine by J. 
Dietrich, by Kohn and by Meyer. 

Therapeutics. — Aloes, being a stimulating purgative, is chiefly 
used in the constipation of atonic subjects. In the constipation of 
plethora it should not be employed; neither should it be administered 
when active abdominal or rectal inflammation exists. During preg- 
nancy it is best avoided, and large purgative doses should never be 
given. Formerly it was taught that aloes should not be used in 
hemorrhoids; but most, if not all, of the cases of this affection depend 
upon a condition of relaxation of the rectal veins, and Fordyce Barker 
insists upon the great value of aloes in piles, and states that Oppolzer 
was especially famous for his treatment of this affection, and that his 
prescriptions were, when piles are associated with constipation, aloes 
and quinine; without constipation, aloes and sulphate of iron. When 
costiveness accompanies atonic amenorrhea, aloes alone of all the 
laxatives should be exhibited; and it is also of service in atonic 
menorrhagia. 

SENNA. 

Under the name of Senna various species of the genus Cassia have 
found their way into commerce, but at present the U. S. Pharmaco- 
poeia recognizes only the leaflets of the Cassia acutifolia of Nubia and 
Upper Egypt (Alexandria Senna), and of the Cassia angustifolia of 
Southern India (Tinnevelly Senna). The senna-leaves vary from 
three-fourths of an inch to an inch and a half in length, and are to be 
distinguished by the inequality of their bases, the two sides of the 
lamina or leaf-blade joining the midrib at unequal heights and angles. 
Senna depends for its activity upon the presence of the glucosides 
chrysophan and emodin. Cathartic acid which has been described as 
its active principle is apparently not a pure principle. 

Official Preparations : 

Confectio Sennse (10 per cent.) 1 to 2 drachms (4-8 Gm.), 

Pulvis Glycyrrhizse Compositus (18 per cent.) J to 1 drachm (2-4 Gm.). 

Fluidextractum Sennse \ to 1 fiuidrachm (2-4 C.c). 

Syrupus Sennse (25 per cent.) 1 to 4 fluidrachms (4-15 C.c). 

Infusum Sennas Compositum (Black Draught) 

(6 per cent.) 4 to 6 fluidounces (120-180 C.c). 

Therapeutics. — Senna is a very powerful, somewhat irritating 
hydragogue cathartic, acting, it is said, as readily upon swine, dogs, 
cats, and horses, as upon man. When given alone, it is very apt to 



CATHARTICS 



507 



gripe Beverely, and is consequently more often used In combination, 
[n obstinate fecal accumulation the Black Draughl constitutes a most 
efficient and safe remedy. 

In small doses it is often used as a laxative. Its infusion injected 
into the veins is said to cause both vomiting and purging, and the 
milk of nursing women taking it is affirmed to acl as a cathartic. An 

aromatic should he administered with senna, to lessen its tendency to 
gripe. The confection is a very complex but elegant preparation, 
used only as a laxative, especially in pregnancy; it is not suited to 
dyspeptic cases, on account of its tendency to derange the digestion. 
The compound infusion contains manna and magnesium sulphate, 
causes very large watery discharges in dose of four fiuidounces (120 
C.c.), and is often used in fecal impaction. 



RHAMNUS. 

Two species of the genus Rhamnus, the Rhamnus Frangula or 
buckthorn, and the llhanmus Purshiana, California buckthorn, are 
recognized by the Pharmacopoeia. The former, however, is but little 
used in this country. The California buckthorn is a small tree which 
is found on the Pacific coast from California to Oregon. The official 
portion of the plant is the bark which is commonly called Cascara 
Sagrada (Sacred bark). It is one-sixteenth to one-eighth of an inch 
thick and usually occurs in the form of quills from two to four inches 
long. The outer surface is gray, the inner surface brown. The taste 
is bitter and nauseous. Its activity is due to a glucoside variously 
known as purskianin or cascarin, which yieldson decomposition emodin. 
The bark, when fresh, also contains a ferment which causes much 
griping. The Pharmacopoeia, therefore, directs that it should at 
least be one year old before being used. 

Official Preparations : 

Extractum Rhamni Purshiana? 2 to 5 grains (0.12-0.3 Cm.). 

Fluidextractum Rliamni Purshiana; J to 2 fluidrachms (2-8 C.c). 

Fluidextractum Rhamni Purshiana; Aromati- 

eum $ to 2 fluidrachms (2-8 C.c). 

Fluidextractum Frangulae 15 minims (1 C.c). 

Cascara sagrada differs from most of the cathartics in the fact 
that there is apparently no tendency to constipation consequent to 
its use; on the contrary, it frequently seems to act as. a tonic to the 
bowel, restoring its motor function and is, therefore, frequently 
employed as a laxative in habitual constipation. 

Phenolphthalein. — This substance which has long been familiar 
to chemists, as an indicator for alkalies, has been recommended by 
Tunnicliffe and others as a pleasantly acting laxative. In doses of 
from 2 to 5 grains (0.1-0.3 Gm.) it causes large mushy stools without 
much griping. 

If used too freely it is not entirely devoid of toxic properties. 



508 LOCAL REMEDIES 

Bile. — The United States Pharmacopoeia recognizes crude Oxgall, 
the fresh bile of Bos taurus, and prepares from it by means of 
alcohol Fel Bovis Ptjrificatum (Purified Oxgall), a yellowish-green, 
soft solid, having a peculiar odor, and a partly sweet and partly 
bitter taste. It is very soluble in water and in alcohol. 

There is much experimental evidence to show that oxgall is the 
most powerful stimulant we have to the secretory activity of the liver. 
Schaeffer, however, believes that this substance does not have a direct 
stimulant action upon the liver but that its effects are due simply 
to the offering for absorption a preformed constituent of the bile, 
because he found that the amount of bile solids passed out after the 
exhibition of oxgall did not exceed the normal plus the amount which 
had been artificially exhibited. 

When taken internally, in large doses, it is a feeble laxative and 
there is some clinical evidence in favor of the belief that, in that 
condition known as chronic biliousness, full doses of oxgall often act 
very favorably. We have also used it in catarrhal jaundice with appar- 
ent excellent results. Dose, five to twenty grains (0.3-1.3 Gin.). 

SALINE CATHARTICS. 
Under the term of salines are included certain salts of the earthy 
metals, which because of their slight absorbability from the intestinal 
tract disturb the osmotic balance between the bowel contents and the 
surrounding tissues. In the majority of instances the ion determining 
the cathartic action is the acid radical, although certain bases, notably 
mercury and magnesium, seem to possess cathartic properties. The 
laxative salts are those of sulphuric, phosphoric, citric and tartaric 
acids. The official salts of this class are: sodium sulphate, phosphate, 
and citrate; magnesium sulphate and citrate; sodium and potassium 
tartrate; potassium citrate and potassium bitartrate.* 

Official Saline Cathartics : 

Magnesii Sulphas [Epsom Salts] 4 drachms (15 Gm.). 

Magnesii Sulphas Effervescens (50 per 

cent.) 1 ounce (30 Gm.). 

Sodii Sulphas [Glauber's Salt] 4 drachms (15 Gm.). 

Sodii Phosphas 1 to 2 drachms (4-8 Gm.). 

Sodii Phosphas Effervescens (20 per 

cent.) 4 drachms (15 Gm.). 

Sodii Phosphas Exsiccatus \ drachm (2 Gm.). 

Potassii et Sodii Tartras [Rochelle Salt] . .2 to 4 drachms (8-15 Gm.). 

Potassii Bitartras [Cream of Tartar] i to 1 drachm (2-4 Gm.). 

Pulvis Effervescens Compositus [Seid- 

litz Powder] 1 pair of powders. 

Potassii Citras 15 to 45 grains (1-3 Gm.). 

Potassii Citras Effervescens (20 per cent.) 1 drachm (4 Gm.). 

Liquor Potassii Citratis (8 per cent.) i to 1 fluidounce (15-30 Gm.). 

Liquor Magnesii Citratis 4 to 8 fluidounces (120-240 C.c). 

Liquor Sodii Phosphatis Compositus 1 to 2 fluidrachms (4-8 C.c). 

* The natural laxative waters, as those of Carlsbad, Saratoga Vichy, Kissingen, etc., are simply 
mixtures of these drugs with other salts, usually including large quantities of sodium chloride. 
(Formulae for making these salts are in the National Formulary.) 



I \ III AIM ICS 



:,()'.) 



The presence of one of these Baits in the intestines, because it 
does qoI easily pass through the intestinal wall, not only prevents Hie 
absorption of water from the intestine bul also encourages the passage 
of water from the surrounding tissues into the bowel by osmosis. It 
does noi seem likely, however, thai the pouring of fluid into the 
intestinal tract is the result solely, or even chiefly, of osmotic pressure, 
hut that is still more dependent on a true stimulant influence on the 
intestinal glands. The investigations of .Matthew Hay, although 
Carried OUt many years ago. still remain the most probable expression 
of the mode of action of the saline cathartics. This author concluded 
that: 1. A saline purgative always excites more or less secretion in 
the intestines due to bitterness and specific properties of the salt 
rather than to osmosis; 2. the low diffusibility of the salt impedes 
the absorption of fluid; :>. between stimulated secretion on one hand, 
and lessened absorption on the other, there is an accumulation of 
fluid in the bowel; 4. the accumulated fluid partly from ordinary 
dynamic laws, partly from a gentle stimulation of peristalsis, reaches 
the rectum and produces purgation. 

While there is some diversity of opinion as to which one of the 
factors involved in the catharsis is the most important, as far as the 
practical utilities of this group are concerned there is almost complete 
unanimity. The peculiar usefulness of the salines lies in their rapid- 
ity of action, their freedom from irritant properties and the liquid 
character of the stools produced.* 

Four theories as to ihe mode of action of the saline laxatives are extant. These 
arc: First, thai they act by increasing peristaltic activity; second, that they in- 
crease the fluidity of the intestinal contents by tin- process of osmosis; third, that 
they inhibit the. absorption of fluid from the intestines, so making the contents 
more liquid; and fourth, that they directly stimulate the secretory activity of the 
intestinal glands. 

The theory that the salines act solely by increasing the peristalsis is no longer 
tenable, for although l'hiry, Radzicjewski and Schiff fail to obtain an increase in 
the intestinal fluids after ihc administration of these laxative salts, the work of 
Morcau, of Brunton, of Vulpian, of Hay, and of McCallum, proves that there is an 
increase in I he quantity of intest inal contents following the exhibition of these drugs. 

That the augmentation of the fluid in the intestines is not due, at least entirely, 
to a change in the osmotic relation is shown, in the first place, by the fact that the 
comparative [>ower of the various saline laxatives bears no relation to their endos- 
motic equivalent. Secondly, that concentrated solutions of sugar which have a 
much higher osmotic factor than the salines, do not purge, and thirdly that hypotonic 
solutions of these salts ad catharticafly. 

The theory thai these purgatives prevent absorption of fluid has been upheld by 
Schmiedeburg and his pupils, especially Wallace and Cushny. these authors found 
that when a solution of a sulphate, citrate or tartrate, approximately isotonic with 
i he blood, was placed in a loop of intest ine t he fluid was absorbed much more slowly 
,| uin _ hit ion of choride or iodide. This, however, does not show 

that a concentrated solution will not provoke a flow of fluid towards the intestines. 

Ad regards the effect of the salines upon peristalsis, it is very difficult to draw- 
conclusions. Le Gros, Van Braan Houckgesst and Rabouteau all assert that the 
-dines do not increa.se the peristaltic movements of the bowel. Radziejewski finds 



■ idy of rtie pflert of salines on metabolism see London '/.. K. M., \iii. 



510 LOCAL REMEDIES 

that there is a greater peristaltic movement after the exhibition of Epsom's salts, 
and in the investigation of McCallum it was found that sodium citrate, sulphate, 
tartrate, phosphate, barium chloride and magnesium sulphate all produced an 
increase in peristalsis, even when injected subcutaneously or intravenously. Frankl 
was unable to confirm McCallum 's claim tliat the salines purged after intravenous 
injection. 

Magnesium Sulphate (Epsom Salt) ordinarily occurs in small, 
acicular, slowly efflorescent crystals, containing about fifty-one per 
cent, of water of crystallization, soluble in their own weight of water 
at ordinary temperatures. The taste is bitter, saline, and nauseous. 

Physiological Action. — Epsom salt is a most active hydragogue 
cathartic, producing very large watery discharges without causing 
any irritation of the intestines. 

Injected into the blood stream magnesium sulphate is a violent 
poison depressing the heart * (Curci, Recke, Hay, and Matthews and 
Jackson), paralyzing respiration and producing anesthesia (Matthews 
and Jackson and Meltzer and Auer). According to Meltzer and Auer, 
when locally applied, it destroys the conductivity of nerve trunks. 
It has been injected into the subarachnoid space for the production 
of surgical anesthesia (Haubold and Meltzer). These effects are 
probably due to the magnesium ion. 

Ordinarily magnesium sulphate is not absorbed from the intestines 
in sufficient quantities to produce any symptoms except purgation, 
but recorded cases show that the drug is capable of acting as a violent 
general poison. Christison reports a boy, ten years old, killed by two 
ounces, without the induction of purgation. W. Sang reports, as 
caused by four ounces of Epsom salt in a very concentrated solution, 
burning pain in the stomach and bowels, great dyspnoea, and collapse, 
with dilated pupils, muscular relaxation, and finally coma, ending 
in death, without purging or vomiting. In J. H. Neale's case the 
symptoms were violent enteritis, with most alarming heart depression, 
from which, however, the patient recovered. 

Magnesium sulphate is very largely used when it is desired to 
deplete or to promote absorption through the bowels, as in dropsies; 
or to relieve congestion of the bowels themselves, as in enteritis or 
colitis; or when it is necessary to soften down fecal accumulation, 
as in obstinate constipation. M. Luton affirms that ten centigrammes 
(1.53 gr.), administered hypodermically, usually provoke several 
watery stools; but the practice seems to us a very doubtful one. 

Sodium Sulphate (Glauber's Salt) occurs in six-sided, very 
efflorescent, striated prisms, which finally crumble into a white powder. 
It acts like magnesium sulphate, but is more powerful; it is, however, 
little used on account of its extremely nauseous taste. It is the chief 
active principle of many natural purgative waters which are so useful 
in chronic gastric and other abdominal catarrhs with constipation. 

* According to Curci small doses elevate the blood-pressure by stimulating the vaso-motor 
centre. 



CATHARTICS 51] 

Tin- combination of two ounces of sodium phosphate, one-half ounce 
of Bodium sulphate, and one-half drachm of potassium iodide, taken 
in full laxative doses, well diluted, upon rising, is often very efficient 
in such cases as are benefited by Carlsbad waters. 

Sodium Phosphate. — The disodium hydrogen phosphate (Na 2 - 

HPOJ occurs in colorless, transparent crystals, which effloresce 
and become opaque on exposure. It is soluble in ">.. r > parts ol 
water, and has a saline taste, closely resembling that of common 
salt. In large doses it is a mild saline purgative, bul as such is 
not at present very much employed. Sodium phosphate is 11 ver\ 
useful remedy in chronic infantile diarrkaa with intestinal indigestion, 
especially as it occurs in bottle-fed subjects. It appears to have a 
Specific action upon the liver and also upon the intestinal glands in 
general, so thai it is often of great service where there are habitually 
chalky stools or white fluid motions, and in many cases of green stools. 
In chronic hepatic torpor and in catarrhal jaundice it is often used 
with great advantage, and it seems sometimes of value in lithemia. 

In 1S88 Haig affirmed, as the result of his experiments, that sodium phosphate 
has very pronounced effect in increasing the excretions of uric acid. In a subse- 
quent paper, however, ho stated that if the phosphate contain any sulphate, or if it 
U' in the form of the acid phosphate, or meet with an acid in the stomach which 
should make it an acid phosphate, it lias no power in increasing uric acid excretion; 
BO thai it seems to us that at present we cannot consider sodium phosphate as 
having distinct relations with uric acid excretion. 

TARTARIC ACID. 

Tartaric acid occurs as a white powder or in large, bard, trans- 
parent, six-sided prisms, which are pyro-electric and phosphorescent 
when rubbed in the dark, are nearly free from odor, have a very 
sour taste, and are very soluble in water. In the shops the acid is 
almost always kept in the form of powder. Tartaric acid is the acid 
of the grape, and occurs in grape-juice as potassium bitartrate. When 
the juice undergoes fermentation and alcohol is developed, the acid 
-alt. not being soluble in the newly formed menstruum, precipitates, 
collecting as a dark mass in the wine-casks, whence it is sent into 
commerce under the name of argol or tartar. 

Physiological Action. — In powder or concentrated solution tar- 
taric acid is a very decided irritant, capable of producing, when taken 
internally, violent oesophageal and gastric burning, vomiting, and, 
it may be. fatal gastroenteritis.* 

Munch finds that when tartaric acid or citric acid is given it soon appears in 
the urine. H. Bence Jones has found that both citric acid and tartaric acid cause a 
pronounced increase in the acidity of the urine of persons taking them, and are apt 

* Ca.se reported in the Brit. Mrd. Journ., for June, 1893, in which the supposed dose was one 
hundred and eighty (trains. Symptoms: diarrhoea, violent abdominal pains becoming more and 
mure marked, followed by fever, delirium, and death on the seventh day. At the autopsy violent 
inflammation of the whole of the uastro-intestinal tract was found. 



512 LOCAL REMEDIES 

also lo give rise to the presence of free uric acid in the excretion. Unfortunately, 
Jones did not attempt to determine whether the increased acidity was or was not 
due to the presence of the vegetable acid in the urine. It is probably partially burnt 
up in the body and partially eliminated by the kidneys. 

Concerning the physiological action of the therapeutic doses of tartaric acid we 
have no definite information. General clinical experience, in accord with the experi- 
ments of Bobrick (quoted from Husemann), who found (hat very large doses render 
the heart's action weaker and slower, indicates that the drug is a very feeble cardiac 
depressant. 

Therapeutics. — Tartaric acid itself is used only for the purpose 
of making effervescent salts, in combination with the bicarbonate of 
soda. The salts it forms with the alkalies are mildly cathartic, more 
gentle in their effects and more pleasant to take than the sulphates. 

Potassium bitartrate is actively diuretic as well as cathartic and 
is considered among the diuretics (see p. 535). 

Potassium and Sodium Tartrate (Rochelle Salt) is made by 
the addition of sodium carbonate to a solution of potassium bitartrate. 
It is soluble in 1.2 parts of water, and has a slightly saline taste. It 
is a mild saline purgative, decidedly less efficient, but much less 
offensive to the palate, than magnesium sulphate. 

The most agreeable means of administering this salt is in the form 
of the Seidlitz powder (Pulvis effervescens compositus). This comes 
in two packets; the white paper contains about thirty-five grains of 
tartaric acid, the blue paper forty grains of sodium bicarbonate and 
two drachms of Rochelle salt. When they are taken, the powders are 
dissolved separately, the solutions added, and the whole drunk while 
effervescing. One pair of powders is the usual dose; but not rarely 
even two pair will fail to purge. 

Toxicology. — There are, we believe, but three fatal cases of tar- 
taric acid poisoning on record: one reported by Devergie, one by 
Taylor, in which death took place nine days after the ingestion of an 
ounce of the poison dissolved in half a pint of water, and one in which 
half an ounce of the acid was supposed to have been taken. The 
treatment of tartaric acid poisoning consists in the free exhibition of 
magnesia, of lime, of potassium or sodium carbonate, or of any article, 
such as soap, containing an alkali in a suitable shape, which may be 
at hand. The after-treatment is that of toxic gastro-enteritis. 

CITRIC ACID. 

Citric acid is the acid of lemon- and lime-juice. It occurs in rhom- 
boidal prisms, of a sour, almost corrosive, taste, extremely soluble in 
water. Lemon juice contains from seven to nine per cent, of citric acid. 

Official Preparations : 

Acidum Citricum 5 to 10 grains (0.3-0.6 Gm.). 

Limonis Succus § to 1 fluidounce (15-30 C.c). 

Syrupus Acidi Citrici (1 per cent.) Used as a vehicle. 

Liquor Magnesii Citratis 8 fluidounces (240 C.c). 

Potassii Citras 20 to 30 grains (1.3-2.0 Gm.). 

Liquor Potassii Citratis (8 per cent.) J to 1 fluidounce (15-30 C.c). 



CATHARTICS 618 

Physiological Action. Citric acid in concentrated form is actively 
irritant, bul less so than tartaric acid. Serious poisoning by it IS 
vcr\ rare, and we know of but one recorded fatal case (II. kionka). 

In Kionka 's Oase, a girl i<> Order to produce abortion took an unknown quantity 
of citric acid, and was brought dying into the hospital with the only clinical record 
th.it she had vomited greatly. Nino thousand four hundred and fifty-two grains of 
citric acid were collected from her gastro-intestinal tract. Marked evidences of 
violent gastritis were present, with gross evidences of hepatic degeneration. In the 
experiments of Maass citric, acetic, and tartaric acid were found to have very little 
influence on frogs unless in large quantities. 

Hugo Schulz states that citric acid is an active antiseptic, a five- 
per-ccnt. solution being sufficient to preserve small pieces of meat 
for two weeks: one part in a thousand was fatal to paramecia. 

Therapeutics. — Lemon-juice is a valuable remedy, but how or 
why it acts is at present entirely unknown. Neither citric acid nor 
any of its known salts act in disease as does the juice of the fruit. 
The chief and most important use of lemon-juice is in the cure and 
prevention of scurvy. During the disease three or four ounces may be 
given three times a day. As a prophylactic against the disease, 
lemon-juice is simply invaluable; but it is absolutely necessary that 
it be of gooci quality. In acute rheumatism, benefit may be derived 
from the free use of lemon-juice, as originally proposed by Rees, of 
London. One or two ounces of it may be given four or five times a 
day; but it is certainly less efficacious than the alkalies. In catarrhal 
jaundice and in habitual torpor of the liver the free administration of 
lemon-juice often aids in effecting a cure. In fevers, lemonade is a 
very refreshing and useful refrigerant drink. 

The neutral citrates are the mildest of the group of saline laxatives. 
The only one which is used to any considerable extent as a laxative 
is the magnesium citrate, although both the sodium and potassium 
salt possess some laxative powers. (For a study of potassium citrate 
see p. 535.) 

Solution of Magnesium Citrate is prepared by putting into a 
strong bottle a syrupy solution of magnesium citrate containing an 
excess of citric acid, adding potassium bicarbonate, and corking 
tightly. On account of its agreeable taste and effervescence, this 
preparation is much used as a purgative. It is similar to magnesium 
sulphate in its action, but is less efficient, more likely to gripe, and 
more irritating. It ought not to be used in inflammatory affections of 
the bowels. 

MERCURY. 

The only preparations of mercury which are used as purgatives 
are calomel and blue mass. Of these the first is by far the more active, 
and indeed is the only one which can be relied upon to purge. 

The chief interest in the purgative action of mercurials centres in 
the question as to their influence upon the liver. Clinically, there 
33 



514 LOCAL REMEDIES 

seems no room for doubt that the mercurials, and perhaps some other 
cathartics, are capable of increasing the bile in the intestinal tract, 
especially in certain conditions, as that known as biliousness or 
hepatic torpor in which this excretion is lacking. As the whole trend 
of modern pharmacological investigation tends to show that the 
mercurial has no effect upon the liver to cause an increase in the 
secretion of bile, it is probable that the action of this group of 
remedies is a sort of mechanical one, perhaps to cause a contrac- 
tion of the gall bladder and the expulsion of its contents into the 
intestinal tract. 

It does not seem necessary to review in detail the large number 
of investigations concerning the action of drugs upon the flow of bile. 
A complete reference to the older literature upon this subject may be 
found in the 13th edition of this book. Suffice it to say, for the present 
purpose, that it seems to have been demonstrated by Stadelmann and 
his pupils that neither calomel nor any of the ordinary cathartics 
distinctly increase the secretion of bile. 

As a result of much investigation and controversy it seems, to-day, well estab- 
lished, that the number of substances which produce an increased secretion of bile 
is comparatively small and does not include any of the cathartics. The most active 
stimulant of biliary secretion is bile itself. Sodium salicylate also seems well estab- 
lished as a biliary stimulant although inferior in power, and according to Kionka 
sodium benzoate and colchicin also increase the biliary flow. 

The older investigations on this subject are open to serious objections. For 
instance, Rutherford, who found a marked increase in the biliary flow as a result 
of a considerable number of substances, mixed bile with his drugs to facilitate 
absorption, ignorant of the fact that the bile itself was a powerful stimulant to the 
secretory activity of the liver. 

Rosenberg found that in dogs sodium salicylate increased the quantity and 
diminished the consistency of the bile; that turpentine had a slight stimulant 
power; while the Carlsbad salts seemed to decrease rather than increase the biliary 
flow. Neutral oils had a much greater power of stimulating biliary secretion than 
any other food or drugs, with the single exception of oxgall. 

Stadelmann, in a series of apparently careful experiments on dogs, found that 
water, whether hot or cold, had no influence upon the amount or fluidity of the 
bile. Alkalies, including the sodium chloride, sulphate, bicarbonate, and phos- 
phate, and many potassium salts, artificial Carlsbad salts, Epsom salts, and many 
other alkaline salts, never caused any distinct increase— indeed, in most of them 
there was apparently a lessening — in the secretion of the liver. Purgatives, in- 
cluding gamboge, jalap, convolvulin, rhubarb, aloes, podophylhn, calomel, etc., 
were equally without distinct effect. Diarrhoea of itself had no influence on the 
amount of bile. Atropine very distinctly, pilocarpine, alcohol and olive oil less 
distinctly, lessened the flow of bile. Antifebrin, antipyrine, caffeine, santonin, 
and oil of turpentine, had a feeble cholagogic action. The only substances 
which were found to possess any certain or powerful influence in increasing the 
flow of bile were the salicylates, bile itself, or bile salts. 

These facts, determined in the lower animals, seem to hold true also for man. 
In a case of biliary fistula, Pfaff and Balch foimd that the biliary secretion varied 
extraordinarily and inexplicably; that it was apparently not affected either by 
calomel or corrosive sublimate; that salol increases the watery flow and the solids 
of the bile distinctly; but that oxgall had a very remarkable effect, increasing the 
amount of the bile as well as the percentage of its solid contents, the biliary acids 
being especially thrown off in extraordinary quantity. On the other hand, in a 
similar case, Wm. Bain reached the conclusion that Kissingen and Carlsbad water, 



CATHARTICS . r >i- r > 

euonymin, Bodium benzoate and sodium salicylate increased both the amount <>f 
bile and its solids while podophyllum resin increased the solid but not the fluid 
portion of the bile. 

Therapeutics. — A mercurial purge is especially indicated by the 
congeries o( symptoms known as biliousness: a heavily coated tongue, 
bitter, disagreeable taste, severe headache, depression of spirits, loss 
of appetite, slight nausea, and light-colored passages. It should be 
borne in mind that one or several of these symptoms may be absent 
in any individual case. Of all single indications for the use of calomel, 
the occurrence of potter's-clay-colored passages is the most important; 
and if such stools exist, and do not depend upon an organic cause, 
repeated small doses of the mercurial should be given, whether there 
be constipal ion or diarrhoea. 

In bilious fever, — i.e., malarial fever with congestion of the liver, — 
a mercurial purge, or several mild mercurial purges, will often, by 
exciting I he action of the hepatic gland, be of great service in preparing 
the way for or aiding in the action of quinine. In catarrhal jaundice, 
mercurials, on the whole, offer, we think, the most frequently success- 
ful mode of treatment. It is evident that in such cases calomel does 
good not merely by its cholagogue influence, but even to a greater 
extent by its antiphlogistic power, no doubt lessening the viscidity 
of the secretions and abating the inflammatory action in the hepatic 
ducts. In many instances it is well to exhibit the mercurial in purga- 
tive doses to start with; but the main reliance is to be placed in the 
continuous exhibition of small doses of the drug until the gums are 
rendered slightly sore. Anything like profuse salivation is, of course, 
to be avoided. In dysentery of an acute sthenic type, calomel acts 
as an antiphlogistic and as an alterative, not only to the liver, but to 
all the intestinal glands. It is possible that it acts also as a bactericide, 
since N. P. Wassilieff has found that although it has no effect in check- 
ing the action of the digestive ferments, it has a very pronounced 
influence in stopping putrefactive changes in food by killing the 
organisms which produce such changes. 

RESINOUS CATHARTICS. 

As already stated, most of the cathartics of this group are intensely 
irritant and belong to the old class of drastic purgatives; many of 
them are capable of causing fatal gastro-enteritis. Euonymus and 
leptandra are, however, comparatively mild in their action. The 
group is characterized by containing irritant resins for their active 
principles, these resins are usually glucosidal and more or less 
closely related to each other in chemical as well as physiological 
properties.* 

Croton oil. which on account of its irritant properties is clinically related to this group, is 
considered under the head of cathartic oils. 



516 LOCAL REMEDIES 

JALAP. 

The tuberous root of Exogonium Purga, a convolvulaceous vine 
growing in Mexico. Jalap comes into the market in two forms: one, 
that of the younger roots, which are sold undivided; the other, that 
of the old roots, which are brought into the market in transverse or 
longitudinal slices and in pieces. The first variety consists of very 
hard, irregularly globular, brittle roots, about the size of a fist, or 
smaller, and often slashed with vertical incisions, made for the pur- 
pose of facilitating drying. Jalap contains a resinous glucoside 
convolvulin and a smaller quantity of another resin which appears to 
be identical with scammonin. The Pharmacopoeia requires that it 
contain not less than 7 per cent, of resin. 

Official Preparations : 

Jalapa 10 to 20 grains (0.6-1.3 Gm.). 

Resina Jalapae 2 to 4 grains (0.12-0.25 Gm.). 

Pulvis Jalapae Compositus (Jalap 35, Potas- 
sium Bitartrate 65) $ to 1 drachm (2—4 Gm.). 

Physiological Action. — Upon dogs and horses jalap (Still6) is 
said to act as a powerful hydragogue cathartic, and in overdoses as a 
gastro-intestinal irritant. Its active principles are absorbed, since 
Cadet de Gassicourt produced diarrhoea in dogs by the free application 
of jalap to the shaven skin, and J. Muller found the resin in the blood 
of dogs to which he had given it. Stille, however, asserts that it does 
not impart its purgative properties to the milk of nursing women, 
and that in man it is not absorbed by the skin. In man jalap 
produces free hydragogue catharsis, often with nausea; or, if in 
overdoses, violent vomiting and purging. 

Therapeutics. — Jalap is especially indicated when it is desirable 
to produce large watery stools. It is, however, very rarely used 
alone. A favorite combination with many practitioners is of it and 
calomel. In the form of the compound powder jalap is very frequently 
used with great advantage in ascites and also in other forms of general 
dropsy. It is believed when given in this way to exert some influence 
upon the renal functions: for very many cases the proportion of 
potassium bitartrate in the official compound powder is too small. 

COLOCYNTH. 

The fruit, deprived of its rind, of Citrullus Colocynthis, or bitter 
cucumber, a vine growing in South Africa, Japan, Syria, Egypt, 
Turkey, the islands of the Grecian Archipelago, etc. The fruit is a 
round gourd, from two to four inches in diameter, of a whitish or 
pale yellow color. It occurs in the market with or without its rind. 
The pulp is dry and membranous, whitish, and contains the active 
purgative glucoside colocynthin, first discovered by Herberger. 



CATHARTICS 



517 



Official Preparations : 

Bxtractum Colocynthidia 3 to S grains (0.2 o.:? Gm.). 

Extractura Colocynthidia Compositum (Kx- 

traet of Colocynth Hi, Purified Aloes 50, 

Resin of Scammony it. Cardamom (>, 

s»ap II) I to 3 grains (0.06-0.2 Gm.). 

Pilulffl Cat hart ica- Composite (each pill 

contains Compound Extract of Colocynth 

0.08 Ciiii., Calomel 0.0(5 Gm., Resin of Jalap 

0.02 Gm., Gamboge 0.015 Gm.) 1 to 3 pills. 

Pilulffi Cathartics Vegetabiles (each [till con- 
tains Compound Extract of Colocynth 0.00 

Gm., Resin of Jalap 0.02 Gm., Resin of 

Podophyllum 0.015 Gm., Extract of Lep- 

tandra 0.015 Gm., Extract of Hyoscyamus 

0.03 Gin., Oil of Peppermint 0.015 Gin.) t to 3 pills. 

Colocynth in large dose is an irritant hydragogue cathartic, capable 
of destroying life, and, according to Orflla and Schroff, acting upon 
the lower animals as upon man. Christison records the death of a 
woman twenty-four hours after taking a teaspoonful and a half of 
the powder. Roques chronicles a fatal result produced by less than 
a drachm of the powder in decoction, but, on the other hand, narrates 
a case in which three drachms failed to kill (Husemann), and W. A. 
Rolfe reports recovery after a quarter of an ounce of the powdered drug 
in which, although pregnancy existed, abortion was not produced. 

Administration. — It should not be used in dropsy, and is 
employed almost solely in combination with other purgatives. 

SCAMMONY. 

A resinous exudation from the root of Convolvulus Scammonia, a 
vine growing in Syria. It is said to be obtained by cutting off the 
root obliquely about two inches from the origin of the stems, and 
catching in shells the few drachms of milky juice which exude from 
each root. From these shells it is emptied into a vessel and allowed 
to concrete. It occurs in pieces of various sizes of a brownish-green 
color and a peculiar odor like that of old cheese. Scammonin, the 
active resin of scammony, is believed to be identical with jalapin, 
originally separated by Mayer from male jalap, and closely allied to 
convolvulin of true jalap. Therapeutically scammony acts like jalap, 
but is somewhat more irritating. It is almost solely used in combina- 
tion with other cathartics, and on account of its frequent adulteration 
should be given in the form of the resin (Resina Scammonii). Dose, 
from two to five grains (0.13-0.3 Gm.). 



PODOPHYLLUM. 

The rhizome of Podophyllum peltatum, or May-apple, a perennial 
herb, growing in the Northern and Middle United States. Podophyl- 
lum occurs in simple or branched, cylindrical, brownish pieces, about 
the thickness of a goose-quill, smooth or wrinkled longitudinally, 



518 LOCAL REMEDIES 

often obscurely marked with the scars of leaf-scales, and furnished 
with numerous rootlets or their remnants attached to the lower 
surface. The taste is bitterish, acrid, and nauseous. The rhizome 
contains the alkaloid berberine, but the purgative power resides chiefly 
in podophyllotoxin* of Podwyssotzki, although it is probable that 
there are other purgative substances in the rhizome, especially an 
uncrystallizable resin, podophylloresin. 

Podophyllum is a rather slowly acting, but very thorough cathartic, 
whose large dose either in man or in most of the domestic animals 
produces violent purging, with great pain, and often with vomiting; 
the symptoms increasing, if the dose have been sufficient, to excessive 
hypercatharsis, with bloody stools, great prostration, and death. It 
is said to act when given hypodermically. A child four years old was 
killed by an unknown amount. The symptoms were repeated vomit- 
ing, slight purging, collapse, and finally coma, ending in epileptiform 
convulsions (T. G. Morton). An infant twenty-two months old 
recovered from four grains. f 

Official Preparations : 

Resina Podophylli tV to J g'" ain (0.005-0.01 Gm.). 

Pilulse Podophylli, Belladonnae et Capsici 

(Each \ grain of Resin) 1 pill. 

Fluidextractum Podophylli 8 minims (0.5 Co.). 

In therapeutic doses it is believed by very many practitioners to 
act especially upon the liver, and is much used in acute constipation 
and in so-called bilious attacks. As ten or more hours are usually 
required for its action, it should not be combined with quick cathartics. 
With calomel it acts very well. The only preparation that should be 
used is the resin or podophyllin. 

ELATERIUM. 

A substance deposited by the juice of the fruit of Ecballium Ela- 
teriUm, or squirting cucumber, a native of Greece, but cultivated in 
England. In the interior of the ovate fruit is an elastic sac, which 
contains the seeds, and at ripening becomes so distended with juice 
that when the fruit falls off the vine, and the support is removed from 
the stem end, a rupture occurs at the latter position, and the liquid 
with the seeds is forcibly projected. The medicinal principle is said 
to be contained only in this inner juice. In order to avoid loss, the 
fruit is picked with a piece of the stalk adherent to it before ripening, 
and is opened by slicing. Elaterium occurs in light, friable, slightly 
incurved, greenish-gray cakes about a line thick. The taste is acrid 
and bitter, the fracture finely granular. Owing to the variability 



* Podophyllotoxin was believed by its discoverer to be composed of picropodophyllin in com- 
bination with podop)iyllinic acid. Later chemical researches indicate, however, that these sub- 
stances are decomposition products. Podophyllotoxin appears to be a very irritant, active cathartic, 
and has been used in medicine in doses of one-fifteenth of a grain. According to J. Neuberger 
(Arch. f. Exper. Path. u. Pharm., 1890, xxviii.), it causes in the lower animals violent purging and 
severe nephritis, with fall of the arterial pressure and death from exhaustion. 

t Australasian Med. Gaz., ii. 237. 



CATHARTICS 519 

ot' commercial elaterium, the V. S. Pharmacopoeia now recognizes 
only the active principle, Elaterin, which was first separated in a 
pure state by Morries. It crystallizes in colorless, shining, rhombic, 
six-sided, odorless tables, of a very bitter sharp taste and neutral 
reaction. 

Official Preparations: 

Klaterinum 2V *° rV g ra ' n (3-5 Milligm.). 

Trituratio Elaterini (10 per cent.) i grain (0.03 Gm.). 

Physiological Action. — Locally applied, elaterium is a very de- 
cided irritant, producing, according to Pereira, ulcerations in the 
lingers of those who handle the fruit and prepare the drug for market. 
When taken internally, it acts on man as a most powerful hydragogue 
cathartic. 

Kohler has proved that in animals elaterium is absorbed, even 
when given by the mouth, since he found it in the urine of poisoned 
dogs and rabbits. 

Therapeutics. — Elaterium is certainly the most efficient of all the 
hydragogue cathartics, producing in properly regulated doses the 
freest evacuations with comparatively little pain and irritation and 
is much used in the treatment of general dropsy or ascites. As, how- 
ever, its action is very exhausting, great care should be exercised 
not to give it in too large doses, and also to support the strength of 
the patient during the period of purgation, and afterwards, by alco- 
holic stimulants, easily digested nutritious food, and appropriate 
hygienic measures. In the latter stages of dropsy the injudicious 
use of elaterium may cause a fatal exhaustion. For the asserted 
power of elaterium in increasing the intestinal elimination of urea 
we have been unable to find authority. Clinical experience has, 
however, demonstrated the value of elaterium in uremia. In order 
to deplete, elaterium has been employed in various diseases; but this 
use is not to be encouraged, and especially when there is any gastro- 
intestinal irritation or inflammation are the salines much preferable 
to elaterium. 

Elaterium is without doubt capable of destroying life, but we 
know of but one recorded death, — that of a woman in whom two and 
two-fifths grains of the extract of elaterium and sixteen grains of 
rhubarb caused uncontrollable vomiting and purging, ending in a 
fatal gastro-enteritis.* 

GAMBOGE. 

A gum resin, obtained in Siam by breaking off the leaves and 
young shoots of the tree known as Garcinia Hanburii and catching 
in suitable vessels the juice as it drops. When the receptacles consist 
of hollow bamboos, the juice hardens into cylindrical casts, striated 
externally, and with a central cavity due to the loss of substance in 

* See Beck's Medical Jurisprudence, 12th e<l., ii. 719. 



520 LOCAL REMEDIES 

drying. This is the so-called pipe gamboge. Gamboge in sorts occurs 
in irregular masses. Gamboge is a hard, resinoid substance, of a 
brittle, often conchoidal fracture, of a deep reddish-orange color on 
exposed surfaces, more yellowish when freshly broken, affording a 
bright yellow powder, insoluble in water, with which it forms, however, 
a bright yellow emulsion. It has little or no taste, but when chewed 
produces, after a time, an acrid sensation in the fauces. 

Physiological Action. — Gamboge acts upon man as a violently 
irritant cathartic. On the lower animals it has a similar influence, 
but Schaur and Orfila state that when in large dose it often fails to 
purge, producing rapidly fatal gastro-enteritis, so intense as seemingly 
to paralyze the bowels. According to Daraszkiewicz and to Schaur, 
in order for gambogic acid to act as a purgative the presence of bile 
in the intestine is necessary. Schaur and Richter affirm that gamboge 
upon raw surfaces acts simply as an irritant: further, Gmelin and 
Tiedemann assert that they have found its principles in the urine; 
it may therefore well be that solution by the alkaline fluids of the 
intestines is necessary for its purgative action. Lewis, Abeille, and 
Ferriar state that, when given in certain ways, gamboge acts as a 
decided diuretic. If this be true, absorption of its active principle 
must occur. Schaur was not able, however, to detect it in the urine 
of persons or of animals taking it. Even when he injected large quanti- 
ties of it into the blood of dogs he failed to find it in the urine, although 
he did obtain a resinoid substance which he believes to be a derivative. 

Gamboge is so irritant that it is used in practical medicine only 
to give sharpness to purgative combinations. The full purgative 
dose would be from two to five grains (0.13-0.3 Gm.). 

Etjonymus, or Wahoo, the bark of Euonymus atropurpureus, contains a glu- 
cosidal resin, euonymin, which is stated to have a digitalis-like action on the heart. 
Wahoo was found by Noel Paton, when given to dogs in small dose, to increase 
greatly the elimination of urea and uric acid, and by Rutherford to be in large dose 
an active cholagogue in dogs. In man its effeets are often most happy in cases of 
habitual constipation and hepatic torpor. It acts very slowly and purges only moder- 
ately. The dose of the extract (Fltjidextractum Euonymi) is eight minims 
(0.5 C.c); of its extract (Extractum Euomymi) (the best preparation), two to 
four grains (0.13-0.26 Gm.): in cases of dyspepsia it may be repeated with good 
results two or three times a week. 

Leptandra. — The rhizome and roots of Veronica virginica, when given in a 
fresh state, are apparently cathartic, but in their officinal dried form are mild and 
less certain. The active principle seems to be the glucoside leptandrin. Leptandra 
is believed by various practitioners to have special cholagogue properties, and in 
Rutherford's experiments upon dogs the impure resin acted feebly upon the 
liver. The U. S. Pharmacopoeia recognizes the fluidextract (Fluidextractum 
Leptandri). Dose, one-half to one fluidrachm. 

CATHARTIC OILS. 

Ordinary oleic acid has a mildly laxative effect and for this reason 
olive oil and soap are occasionally employed in the lighter forms of 
constipation. The closely allied bodies, however, known as croton- 



CATHARTICS 521 

oleic acid and ricinoleic acid are actively purgative. Apparently the 
oils themselves, i.e., tin. 1 glycerides of these acids, arc not cathartic, 
only the tree acid being active. In the case of croton oil there is 

present with the oil a certain amount of free crotonoleic acid, the 
drug, therefore, acts quickly and also exercises its irritant action 
upon the stomach. In the case of castor oil, however, the free acid 
is not naturally found and the remedy becomes active only after 
saponification which takes place in the intestinal tract; therefore it 
acts more slowly and has no irritant effect upon the stomach. 

CASTOR OIL. 

A fixed, nearly odorless oil, of a nauseous taste, obtained from the 
seeds of Ricinus communis, a shrub native to India, by expression. 
The seeds are slightly warmed before being put under pressure, so 
as to liquefy their contained oil; and the crude oil obtained from them 
is boiled with a small amount of water, so as to coagulate its albumi- 
nous impurities. Castor oil is remarkable for being soluble not only 
in ether, but also in alcohol. The castor-oil seeds, or beans, as they are 
commonly called, contain an acrid, violently poisonous principle, ricin* 

Physiological Action. — Castor oil acts upon the human organism 
as a mild but decided purgative, producing copious fluid fecal dis- 
charges, and in overdoses sometimes vomiting, and always purging 
freely. The bulk of the castor oil is ricinolcin, a glyceride of ricinoleic 
acid, which appears to be the purgative principle, and to be absorbed; 
at least Canvanet affirms that in children castor oil sometimes purges 
when rubbed upon the skin of the abdomen, and when taken into 
the stomach it has been known to exude from the skin. J Buchheim, 
although he submitted the passages produced by the oil to care- 
ful chemical manipulation, failed to detect it or any derivatives. 
According to the experiment (quoted by Stille) of Hale upon himself, 
half an ounce of castor oil injected into a vein produces malaise, 
nausea, faintness, anxiety, and general dulness and depression, 
without purging. 

Therapeutics. — On account of the mildness of its action and a 
special property of soothing an irritated bowel, castor oil is constantly 
employed whenever it is desired simply to evacuate the intestinal 
canal; not so much, however, in chronic constipation as when a 
temporary action is alone required. In various inflammatory or 
irritative affections of the alimentary canal, castor oil is often of the 
greatest service. This is especially seen in the acute diarrhozas and 

* Three beans have caused death in the adult. The symptoms, which do not usually come on 
until from two to five hours, are severe abdominal pain, violent vomiting and purging, which after 
a time may become bloody, collapse, severe muscular cramps, cold sweating skin, contracted 
features, thirst, restlessness, and small rapid pulse. After death, intense redness and even abrasion 
of the stomach and of the small intestine are found. After the stomach and large intestine have 
been thoroughly washed out with warm water, the treatment of castor bean poisoning is that of 
toxic gastro-enteritis, — namely, the use of opium, leeches, ice, demulcent drinks, counter-irritation, 
etc. See Kobert and Stillmark (Arbeiten Pharmah. Inst, zu Dorpal, iii.). 

t See H. Meyer (Arch. f. Exper. Pathol, u. Pharm., 1890, xxviii.). 

j Ward's case (London Med. Gaz., x. 377). 






522 LOCAL REMEDIES 

even in the chronic enteritis of children, but also holds good in the 
diarrhoeas and dysenteries of adults. In chronic pseudo-membranous 
colitis we have seen very excellent results from the long-continued 
daily use of the oil. 

CROTON OIL. 

The fixed oil obtained from the seeds of Croton Tiglium, a euphor- 
biaceous shrub of Hindostan and other portions of Southern Asia. 
This oil is quite viscid, varies in color from a pale yellow to a dark 
reddish brown, and has an acid reaction. Its taste is hot, acrid, and 
extremely persistent; its odor faint, but peculiar. Croton oil consists 
chiefly of the glycerides of ordinary fatty acids, but contains also 
crotonoleic acid, which has been supposed to be its pure active princi- 
ple, but is stated by Dunstan and Boole to be a mixture of inactive 
oily acids with a powerfully vesicating, resinous substance, croton-resin. 

Therapeutics. — Locally applied, croton oil is an intense irritant, 
producing upon the skin an eruption which is at first papular but in a 
very short time becomes pustular.* (See Counter-Irritants.) 
Administered internally, croton oil produces in man and in most of 
the lower animals violent purging, with severe griping, and is capable 
of causing a fatal gastro-enteritis. Its action on the intestine is 
probably in part local and in part through absorption. In the experi- 
ments of Hertwig (quoted by Stille) and of Buchheim, purgation did 
not follow the injection of the oil into the veins of animals; but Con- 
well obtained a result contrary to this, and there is considerable 
testimony that its external use in man is sometimes followed by 
purging (Stille), and even by fatal results. f The experiments of 
Kobert and of Hirschheydt seem to prove that crotonoleic acid is 
both the purgative and vesicant active principle: it exists in the oil 
combined with glycerin. It is believed that the glyceride is slowly 
decomposed in the intestines, and that the acid which is thus set free 
acts progressively. Certainly, Hirschheydt found that pure crotonoleic 
acid, which has appeared in commerce, is not a practical purgative, 
ten milligrammes being very uncertain in their effects, while large 
doses are prone to produce excessive gastro-intestinal irritation. 
Injected into the blood, crotonoleic acid was found to be an exceed- 
ingly active depressant to the circulation. The amount of free cro- 
tonoleic acid in croton oil increases very markedly with age. On this 
account old croton oil, with an acid reaction, acts much more harshly 
than does the recent neutral or nearly neutral oil, and should be 
rejected for internal use. 

Therapeutics. — Croton oil is chiefly used in practical medicine in 
mania, apoplexy, or other diseases in which there is difficulty in 
administering a cathartic. It is also given in cases of very obstinate 
constipation when less active remedies have failed. It is the one 
cathartic employed when, as in some brain diseases, it is desired to 

* For a histological study of the eruption, see Wiener Med. Wochenschr., 1897, xlvii, 1021. 
t See Schmidt's Jahrb., clxiv.; also Robert's Arbeiten, 1890, iv. 45. 



CATHARTICS 



523 



revulse by the intestines. The dose is one drop, in emulsion, or by 
simply placing it upon the tongue. In overdoses, croton oil is ;i 
violent poison. 

Toxicology.— Although in small amounts croton oil causes such 
severe symptoms, yet in larger quantities it has failed to produce as 
serious results as would he naturally expected. It is, however, very 
possible that in at least some of the recorded cases the oil was adul- 
terated. Cowan has reported a case (Husemann) of a child four years 
old who recovered in two days from a teaspoonful of croton oil taken 
on a full stomach; Adams (Husemann) saw recovery in an adult after 
the ingestion of a drachm; and the case is recorded of a woman who 
took about an ounce, was vomited forty-five minutes afterwards with 
mustard, and finally recovered. The minimum fatal dose is not known, 
and probably varies greatly. A child aged thirteen months was killed 
by a quantity believed not to exceed three minims. Giacomini 
(Stille) reports a case in which Iventy-four grains of the drug proved 
fatal in as many hours: although there were but four stools, the 
patient presented the symptoms of general collapse, preserving 
consciousness to the last. A little less than two drachms has caused 
vomiting and death without purging.* 

The treatment of croton-oil poisoning is purely symptomatic. 
Opium should be given to lessen the purging, demulcent drinks to 
lessen the irritation. If collapse develops, cardiac stimulants should 
be administered hypodermically and bodily temperature maintained 
by the application of external heat. 



REFERENCES. 



CATHARTICS. 

Asp Ludwig's Arbeiten, 1868. 

Bain B. M. J., 1898, i. 

Barker Amer. Pract., 1872. 

Brandenburg ...In. Dis., Berlin, 1893. 
Brunton Med. Press and Circular, 

Dec. 31, 1873; Pract., 

May, 1875. 

Buchheim V. A. P. A., xii. 

Bitchheim V. A. P. A., xii. 1. 

Clopatt S. Jb., 1896, ecli. 

Curci L. M. R., Oct., 1886. 

Daraszkiewicz. . .Meletemata de Resinarum, 

Dorpat, 1858. 

Dietrich In. Dis., Dorpat, 1885. 

Dixon B. M., 1902, li. 

Doit Gaz. des Hop., Oct. 24 1885. 

Dhaoendorf and Kubly. . Vierteljahr, fiir 

Prakt. Pharm., xvi. 

Franke A. E. P. P., 1907, lvii. 356. 

Fronmuller Med. Chir. Centralb., 1879, 

xiv. 
Gilbert and Dominici. .C. R. S. B., 1895, ii. 

Groves Pharm. Journ., xvi. 

IIai hulii and Meltzer. J. A. M. A., xlvi. 647. 

Hay J. A. P., 1881-82, xvi., xvii. 

Headland Action of Medicines, London, 

1867, 443. 
Hf.inrichskn S. Jb., ccii. 214. 



Heinze P. N. W., 1903. 

Hiller Z. K. M., 1881, iv. 

Hirschheydt .. . .Robert's Arbeiten, 1890, iv. 

Houckgeest A. G. P., 1872, 266. 

Husemann Handbuch der Toxicologic 

Kionka Z. E. P. T., ii. 9. 

Rleeberg Amer. Med., 1903, vi. 

Kohlstock Charite' Annalen, 1892, xvii. 

Kohn S. Jb., exciv. 246. 

Kohn S. Jb., exciv., 246. 

Legros Gaz. Med., 1873. 

Luton G. H. M. C, 1874, 455. 

Matthews and Jackson 

McCallum On Mechanism of the Physio- 
logical Action of the Ca- 
thartics, Univ. of Cal. 
Pub., 1906. 

Meltzer and Auer. .A. J. P., xv. 387. 

Meyer A. E. P. P., 1890, xxviii. 

Michea L. 1... 1849, i. 15. 

Moreau A. G. M„ 6 s„ xvi. 234. 

Morries Reper. f . Pharm., xxxix. 134. 

Muller In. Dis., Dorpat, 1885. 

Paton B. M. J. 1880, i. 

Pfaff and Balch. J. Ex. M., ii. 

Podwyssotzki. . . .A. E. P. P., xiii. 40. 

Radziejewski. . . . V. A. P. A., 1870, 37. 

Raviart S. M., 1895. 

Recke In. Dis., Gottingen, 1881. 

Regensburger. ..C. M. W., 1877, 328. 



* For cases, see Med. Gaz., xliii.; Ed. M. J., 1861; Lancet. 1870, i.; B. M. J., 1874, i.; Ann. 
d'Hyu.. 1871, i.; also Koberts Arbeiten, 1890, iv.; B. M. S.J., 1868, i. 294; M. T. (/., 1870, i. 



. r )24 LOCAL REMEDIES 

REFERENCES (Continued). 

Rohsxg Strieker's Med. Jahrbuch, Stadelmann B. K. W., xxxiii. 

1873; Exper. Untersuch., Stille Therapeutics, ii. 

u. d., Physiol, der Gal- Stockman- A. E. P. P., xix. 120. 

lenabsond., Vienna, 1873. Thihv Gaz. Mod., 1871; Sb. G. W, I. 

Ruthehfokd Tr. R. S. Ed., xxix. Tot S. M. 1900. 

Sang L. L., 1891, ii. Tunnicliffe N. Y. M. J., lxxvi. No. 12. 

Schiff Nuove Richerehe sul Potere Vulpian Gaz. M^d., 1873, 300. 

Digerente, Morgagni,1867. Wallace and Ansberg. .A. J. P., 1898, i. 411 

Shaffer A. J. P.. xvii. 362. Wassilieff Z. P. C. 1882. 

Smith, T. and H. .Chem. Gaz., 1851. Woroschilskt . . .T. M., xvi. 



FAMILY IV. -DIURETICS. 



While, strictly speaking, the term diuretics refers to those drugs 
which increase the flow of urine, in this chapter are included not only 
these but also drugs which are used for the purpose of affecting the 
mucous membrane of the urinary tract. 

Effect of Water. — The quantity of urine excreted depends to a 
great extent upon the volume of the blood. Any agency, therefore, 
which tends to make the blood more voluminous increases the quantity 
of urine, and, on the other hand, those influences which make the 
blood more concentrated diminish it. For this reason when other 
glands of the body are abnormally active, especially the bowel and 
skin, because of the excess of fluids escaping through these channels, 
the quantity of urine is diminished, and vice versa, a diminution in 
the activity of the sweat glands tends to the production of diuresis. 
Cooling of the surface, therefore, by checking the skin secretions, 
increases the quantity of urine. These facts must be borne in mind 
in using diuretics. Certain drugs, for example pilocarpine, may be 
made to act either as diaphoretics or as diuretics by alterations of 
the temperature of the patient's surroundings. 

Of still greater importance is the introduction of water into the 
system either by having the patient drink freely, or by the injection 
of physiological salt solution. Either of these measures in a healthy 
organism leads to a marked increase in the quantity of the urine 
excreted. 

A matter of great importance in this connection is the effect of 
the ingestion of water upon the elimination of the solid constituents 
through the urine. Although some of the older investigators, notably 
Bocker, failed to obtain any increase in the total amount of nitro- 
genous material eliminated through the use of water, the preponder- 
ance of testimony is so strong that it must be considered as proven 
that, in ordinary conditions, not only the total bulk of urine but also 
the quantity of solid matter is increased by the administration of 
water. Whether this increase of urinary solids betokens a more active 
metabolism, or whether it merely indicates a washing out of already 
formed waste products, cannot be so definitely answered. Meyer, 
Voit, and many others maintain that the increase in solids is simply 
the result of flushing the system and that, if the administration of 
water is continued, the primary augmentation of solid matter gives 
way to a marked decrease in the urinary nitrogen after the accumu- 
lated products of metabolism have been flushed out. On the other 
hand, the experiments of Landauer, and of Edsall, and others, indicate 

525 



526 LOCAL REMEDIES 

strongly that, while the solid matter eliminated is largely stored 
up waste products, there is also a distinct, if slight, increase in the 
destruction of proteid tissues. 

It is evident, from the above, that water may become a valuable 
remedy in the treatment of many conditions of the urinary tract. 
In the first place, frequently it is useful for the purpose of getting 
rid of accumulated metabolic poisons. Thus it is sometimes- of service 
in the treatment of uremia, especially in the more acute types. It 
has, however, a still larger field for usefulness in the excretion of the 
metabolic poisons giving rise to those symptoms commonly spoken 
of as lithemic, — as gout, chronic rheumatism, and the like. 

Again, in cases of suppression of the urine, whether due to the effects 
of irritant poisons or hemorrhage, the administration of fluids is 
frequently of great service in re-establishing the urinary activity. 
In the first case by diluting the blood and hence lessening the con- 
centration of the solution of the irritant, it decreases the irritation 
of the kidney. In the latter case it leads to a filling of the vessels 
which have been emptied by the loss of blood and offers, again, fluid 
for the kidney to excrete. Frequently, also, it is of service to pre- 
vent irritation of the kidney, as in lithemia, by rendering the urine 
more dilute. In the same way it may be used to make the excretions 
more bland in cases of irritation of the bladder. 

For medicinal purposes, water may be introduced into the system 
through one of three channels; the alimentary tract, subcutaneous 
tissue, or intravenous injection. In chronic cases, where the immediate 
effect is not a matter of great moment, for obvious reasons it is gen- 
erally preferable to simply have the patient drink regularly large 
quantities of fluid. Where, however, the condition is more serious 
the fluid may be introduced by hypodermoclysis. For this purpose 
we believe an 0.9-per-cent. solution of sodium chloride is the best. 
This should be warmed to a temperature of about 102° F. and injected 
slowly into the subcutaneous tissue, either of the thorax, abdomen, 
or back. A fountain syringe placed about three feet above the 
patient ordinarily affords sufficient power, and, if the injection is 
carried out carefully, from one-half to one pint of solution may be 
injected in one part without much discomfort. If it is desirable to 
introduce larger quantities the needle should be withdrawn and intro- 
duced into another portion of the body. Needless to say the operation 
should be done with strictest aseptic precautions. In conditions of 
great immediate danger it is sometimes necessary to inject the fluid 
directly into the vein. 

The subcutaneous or intravenous injection of physiological salt 
solution is very largely used in the treatment of conditions not directly 
associated with kidney function. In cases of circulatory failure or 
collapse due to the loss of blood or surgical shock it is a measure of 
great service, for the purpose of maintaining the activity of the heart. 
As a circulatory stimulant in cases of essential heart failure, depend- 
ent, for example, upon cardiac dilatation, or in the presence of cardiac 



DIURETICS 



527 



depressanl poisons, the value of the treatment is far less certain. It 
lias also been recommended, by Delbert and others, in the treatment 
of various forms of poisoning with the idea that it will hasten the 
elimination of the poison. While Delbert has shown that with the 
free intravenous injection of salt solution suprafatal doses of strych- 
nine are borne by the dog without the development of poisoning, it 
is probable that the fluid acts by diluting the concentration of the 
poison in the blood, rather than by increasing its elimination. 

The chief indications for the use of diuretics are as follows: 

1. To maintain the action of the kidneys. It is hardly necessary 
here to discuss the necessity of excretion to the system. In various 
kidney diseases this indication is very urgent; but as the lessened 
excretion too often depends upon a profound organic alteration of 
the renal secreting structure, it is evident that very frequently diuretics 
must fail when most needed. In the great majority of cases in which 
diuretics are used to fulfil the present indication, only the mildest of 
the class should be employed. Whenever there is inflammation of 
the kidneys, even if it be chronic, irritating diuretics should be avoided. 
When lessened urinary excretion is purely functional in its origin, 
diuretics are often most serviceable. In fevers especially is it neces- 
sary to maintain the action of the kidneys; for this purpose water 
should always be freely given during fever. The alkaline diuretics 
sometimes may be exhibited; but the most generally serviceable of 
all remedies of the class in the febrile state is the sweet spirit of nitre. 

2. To evacuate fluid. For this purpose hydragogue diuretics are 
employed in all forms of dropsy. 

3. To soothe and diminish irritation of the genito-urinary organs. 
The value of water in fulfilling this and the next indication has already 
been pointed out. By lessening the acidity of the urine and rendering 
soluble the uric acid which is present, the alkalies are equally important 
in carrying out the present and the following indication. 

4. To alter the urinary secretion so as to prevent the deposition of 
calculous material. Notwithstanding it has been otherwise asserted, 
no practical measure has as yet been devised of dissolving a calculus 
when once formed. Even to alter the urine so as to prevent further 
deposition is probably impracticable, except in cases of uric acid or 
phosphatic diathesis. 

The diuretics may be divided into three groups: 1, Those that 
affect the kidney indirectly by increasing the amount of blood which 
passes through it, in other words the circulatory stimulants; 2, 
those which have a direct irritant or stimulant action upon the 
kidney cells — Stimulating Diuretics; 3, substances which change the 
osmotic relations of the blood — Saline Diuretics. There are also 
included in this chapter certain drugs which are used not so much 
for their effects in increasing the quantity of the urine but for their 
local action upon the mucous membrane of the urinary tract — 
Alterative Diuretics. 



528 LOCAL REMEDIES 

STIMULATING DIURETICS. 

Of the drugs belonging to this group strophantus, apocynum, and 
caffeine are considered in the chapter on Cardiac Stimulants. Any 
locally irritant substance which passes out through the kidney may, 
by its irritant influence, increase the flow of urine. Certain drugs of 
this character, notably oil of juniper, have been used to a considerable 
extent as stimulating diuretics, but, on account of their other 
properties, are considered elsewhere. 

SQUILL. 

The bulb of Urginea maritima, a liliaceous plant growing in the 
south of Europe, especially on the shores of the Mediterranean. The 
bulb varies in size from that of a child's head to that of the fist. It 
is composed of numerous layers or scales, which separate when it is 
sliced for drying. As kept in the shops, squill is in horny flakes, of a 
white or red color, becoming leathery when wet, and having an acrid, 
bitter taste. It yields to water and alcohol and also to vinegar. 

The nature of the active principle of squill has not been established. 
A number of glucosides have been described by chemists, and Merck 
has put upon the market three substances, scillin, scillipicrin, and 
scillitoxin* There is, however, no sufficient proof as to which, if 
any, of these substances represents the crude drug. 

Official Preparations : 

Scilla 1 to 3 grains (0.06-0.2 Gm.). 

Fluidextractum Scillae 1 to 3 minims (0.06-0.2 C.c). 

Tinctura Scillae (10 per cent.) 10 to 20 minims (0.6-1.2 C.c). 

Acetum Scillae (10 per cent.) 10 to 20 minims (0.6-1.2 C.c). 

Syrupus Scillae (4£ per cent.) A to 1 fiuidrachm (2-4 C.c). 

Syrupus Scilla? Compositus (Squill and 
Senega each 8 per cent., tartar emetic fo 
per cent.) [Cose's Hive Syrup] 1 fiuidrachm (4 C.c). 

Physiological Action. — Kidney. — Squill is a stimulant to the 
kidneys, and in overdoses causes an irritation whose result is lessening 
of the secretion, scanty bloody urine, or absolute suppression of urine, 
according to the amount of the poison ingested. Its diuretic action 
has been noted in animals b}^ Schroff and by Chiarenti (quoted by 
Stille), and there can be no doubt as to the power that squill has of 
increasing the watery portion of the urine. We know of no studies 
upon its action on the urinary solids. According to Stille, the external 
application of squill will produce its characteristic effects on the 
system. 

* Fronmiiller has reported (Memorabilien, 1879, xxiv. 250) a series of experiments made, upon 
persons suffering from various ailments, with the scillin, scillipicrin, and scillitoxin of Merck. He 
found that scillitoxin in doses of 0.45 grain acted as a rather uncertain diuretic, and frequently 
caused giddiness, headache, and loss of appetite; scillin seemed to be devoid of diuretic properties; 
while a gramme of a solution of scillipicrin in water (one part in fifty) administered hypodermically 
usually caused a great flow of urine, without other evil symptoms than some smarting at the place 
of injection. 



DIURETICS 529 

Circulation. It is certain that squill contains some substance 
which acts similarly to digitalis on the heart, and that this is to be 
found in the extract . 

C. Lupinski found that scillitoxin is a powerful stimulant to the peripheral vagi 
in the frog, causing slowing of the pulse, and in certain doses diastolic cardiac arrest, 
and in the dog slowing of the heart. Large doses cause in the frog tetanic contrac- 
tions of the heart. He also found that in the dog large doses finally paralyze the 
peripheral vagi and produce a rapid pulse. The arterial pressure is increased, partly, 
it is affirmed, by the increased cardiac energy, and partly by a peripherally produced 
vaso-motor contraction. 

Husemann affirms that the extract has no expectorant properties; that it is a 
digitalis-like, cardiac stimulant, and acts as a diuretic solely by affecting the 
renal circulation. 

Therapeutics. — Squill is a valuable remedy in dropsy when the con- 
dition of the system is atonic and when there is no disease of the kid- 
ney. It may even be used with advantage in serous effusion into the 
pleura or the pericardium dependent upon chronic inflammation of 
the membrane, especially in combination with calomel. A pill of one 
grain (0.06 Gm.) each of squill and digitalis is very efficient in cardiac 
dropsy; sometimes the addition of calomel is advantageous. The 
one contraindication to the use of squill is the existence of Bright's 
disease or of acute irritation of the kidney. 

Toxicology. — In poisonous doses squills causes great abdominal 
pain, violent purging and vomiting, lessened or almost suppressed 
secretion of bloody albuminous urine, with slow pulse, ending, it 
may be, in collapse, convulsions, and death. According to Husemann, 
twenty-four grains of squill have caused death. 

The treatment of the poisoning consists in the evacuation of the 
stomach and bowels by ipecacuanha and castor oil, if nature has not 
already fulfilled the indication; the free use of opium; the exhi- 
bition of large quantities of water, for its action on the kidneys; and 
the usual measures for the relief of gastro-enteritis, if much tenderness 
be present. Early in the poisoning care should be exercised in the 
exhibition of alcoholic stimulants, for fear of increasing the gastric 
irritation; during the stage of collapse they may be imperatively 
demanded, and with their use should be combined that of dry heat 
applied externally, and of the other usual measures of relief during 
collapse. 

Administration. — As a diuretic, squill should be given in solid 
form, one or two grains (0.06-0.12 Gm.) every three hours, the dose 
being gradually increased until some nausea is felt. 

SCOPARIUS. 

Scoparius is the dry tops of Cytisus Scoparius, or the common 
broom- plant of Europe, which is cultivated in this country and has 
in some places escaped from the gardens. It occurs as greenish 
twigs, with minute downy leaves, has a bitter, nauseous taste, and, 
when bruised, a peculiar odor, and yields its virtues to hot water. 
34 



530 LOCAL REMEDIES 

Stenhouse discovered in scoparius a neutralized crystallizable prin- 
ciple, Scoparin, which probably represents the purgative and diuretic- 
influences of the drug, and also a liquid alkaloid, Sparteine. (See 
sparteine sulphate, page 248. 

In overdoses, scoparius causes free purging, and even vomiting; 
but as ordinarily administered it is an efficient hydragogue diuretic, 
which is much used in general dropsy, and is one of the most reliable 
remedies of its class. It is best given in decoction, — half an ounce 
of the tops in a pint of water boiled down to half a pint; of this an 
ounce may be given every three hours until some effect is produced; 
or a fluidextract, which is not official, may be given in half-drachm 
(2.0 C.c.) doses. 

Mercury. — Many years ago therapeutic writers, notably George 
B. Wood, asserted that the combination of digitalis, squill, and 
calomel yields in the treatment of dropsy, and especially of cardiac 
dropsy, diuretic results much superior to either of the vegetable 
products alone; but more recently E. Jendrassik directed attention 
to the great practical value of calomel as a diuretic. 

The present experimental evidence in regard to the effect of mercury upon 
diuresis in the lower animals is contradictory. W. Cohnstein affirms that the hypo- 
dermic injection of the mercurial produces very quick active diuresis in the rabbit, 
but Vejun-Tyrode and Nelson failed to get a consistent diuretic action either in the 
dog, cat, or in the rabbit; as they affirm that "throughout all these experiments 
there were evidences of more or less severe renal irritation as shown by the presence 
of blood and casts and by diuresis, " it is probable that they employed the calomel 
in too large doses. 

According to Brasse and Wirth, when mercury is given hypodermically in large 
dose it soon appears in the urine, which is markedly increased in quantity; if, as 
not rarely happens, the urine becomes albuminous, excretion of mercury at once 
ceases, albumin and mercury never coexisting in the urine. Silva, experimenting 
with defibrinated blood, finds that the addition of a mercuric salt causes the kidney 
vessels to dilate, the local blood-pressure to rise, and secretion to increase. More- 
over, it is certain that mercurials in excess cause desquamative nephritis; so that 
it must be concluded that these preparations either stimulate or irritate the renal 
secretory structure proportionately to the amount present. According to Biegan- 
ski, the diuretic effect is most active after subcutaneous injections and least so 
after inunctions. 

The destruction of renal secreting tissue by disease without doubt 
interferes with the diuretic action of mercurials, but the fact remains 
that in chronic parenchymatous nephritis with alarming decrease in 
the secretion of urine, calomel is one of the most effective diuretics 
known. In cardiac dropsy it is often very efficient in improving not 
only the drops\ r itself but the condition of the digestive organs. In 
some cases of chronic cardiac disease the continued use of minute 
doses of the mercurial is very advantageous, but when it is desired 
powerfully to affect the kidneys large doses of the drug are required. 
Under these circumstances, we have found the administration of five 
grains (0.3 Gm.) of calomel every two hours until fifteen grains (1 Gm.) 
in all are taken to act most happily. It is sometimes, though rarely, 



DIURETICS 531 

necessary to use opium to check the purgative action of the calomel. 
When there is excessive debility some caution may be necessary in 
( his use of mercurials, but we have seen life apparently saved for 
i ho time being by the removal of an acute suppression of urine in 
advanced Bright's disease. 

XANTHIN COMPOUNDS. 

Xanthin, or Dioxypurin, yields the following compounds which 
arc interesting therapeutically: 

First, Trimethylxanthin or Caffeine, which we have already fully 
considered. (See p. 209.) 

Second, three isomeric dimethylxanthins: 

1. — Dimethylxanthin, Theobromine; 

2. — Dimethylxanthin, Theophyllin (Theocin); 

3. — Dimethylxanthin, Paraxanthin. 

Dimethylxanthin or Theobromine has been chiefly used in the 
form of the sodium theobromine salicylate, a white powder, soluble in 
less than half its weight of warm water, and containing about forty- 
nine per cent, of theobromine. It has been put upon the market 
as a proprietary remedy under the name of Diuretin, which, accord- 
ing to analysis, contains from thirty to forty per cent, of theobromine. 
Attention was first called to theobromine as a practical remedy, in 
1890, by C. Gram and Kouindig-Pomerantz. 

Physiological Action. — Theobromine is rapidly absorbed, and 
has been shown by the studies of Albanese, Bondzynski and Gott- 
lieb, and of Kriiger and Schmidt, to be eliminated in part unchanged, 
and in part in the form of methylxanthin.* 

General Effects. — The ordinary dose of theobromine causes no 
distinct symptoms in man, and we know of no recorded cases of 
poisoning by it. According to I. M. Sabashnikoff large doses pro- 
duce in the lower animals a quickening of the respiration, which is 
followed after a toxic dose by intense dyspnoea, high temperature, 
free salivation, vomiting, diarrhoea, and excessive diuresis. The 
elevation of temperature, which sometimes amounts to 4° C., is, 
according to Sabashnikoff, prevented by previous high section of 
the spinal cord. 

The detailed physiological action of the drug has not been worked 
out; according to Sabashnikoff there is increased irritability of the 
motor area of the cerebral cortex, and upon the striated muscles 
the drug acts as does caffeine. The toxic dose lowers the arterial 
pressure. (Cohnstein and Bock.) Cohnstein found that the full 
therapeutic doses had no perceptible influence upon the blood-pres- 
sure, and in Bock's researches the pressure was only elevated occa- 
sionally, the most marked phenomenon being great increase in the 

* The researches mentioned show that the exact form of elimination, as well as the percentage 
of the various educts, varies in different species of animals, and very probably in different individ- 
uals under varying circumstances. In man, 3-methylxanthin seems to be the chief educt, though 
7-methylxanthin (Heteroxanthin) has been found; while in rabbits 7-methylxanthin is especially 
produced. 



532 LOCAL REMEDIES 

frequency of the pulse-rate, probably due to excitation of the accel- 
erator mechanism of the heart, since the vagi was found to be thor- 
oughly active. As the result of studies made upon the isolated heart 
of the mammal, Bock believes the fall of pressure is due to an action 
upon the cardiac muscles, which decreases its elasticity. He also 
believes that the rise of pressure, sometimes produced by the small 
doses, is the result of the increased pulse frequency. 

Kidney. — In the oncometrical studies of Gottlieb and Magnus, 
the increased diuresis was accompanied by an increase of the size of 
the kidney. In the chloralized animal these investigators found that 
the increased diuresis persisted, although the kidney was markedly 
below its normal size, — evidence that the diuresis is the outcome of 
a direct action upon the secretive power of the kidney. 

Therapeutics. — Theobromine has been much used as a diuretic 
which is not irritant to the kidneys, and rarely causes disagreeable 
symptoms. It has been given in acute and chronic nephritis with 
excellent results, and has been especially recommended in cardiac 
dropsy, with the statement that it increases the force and regulates 
the character of the cardiac beat when the heart is weak. (See 
Masius, also Pawinski.) In rare cases it acts unfavorably, causing 
headaches, irregularity of the pulse, vomiting, diarrhoea, and even — 
according to W. Schmieden — hematuria. From eighty to one 
hundred and twenty grains (6-8 Gm.) may be administered during 
the course of the day, in capsules or solution, or hypodermically. 
According to Demme, to a child six years old twenty to thirty grains 
(1.2-2 Gm.) may be given in the twenty-four hours. 

Agurin is a white, slightly bitter powder, freely soluble in water, which is said 
to consist of five parts of theobromine acetate and two parts of sodium acetate. It 
should always be prescribed in the form of the powder, its solution not being stable, 
but should be taken in dilute solution in doses of ten to fifteen grains (0.6-1.0 Gm.) 
three or four times a day. In Mosauer's experiments agurin seemed to be more 
irritant to the kidneys than theobromine. 

Paraxanthin. We have not much information concerning this substance, 
but, according to Dreser-Elberfeld, it acts in a manner similar to theocin, increasing 
the output of urinary solids as much as does that drug, but not having nearly as 
powerful an influence in the excretion of water from the kidneys. 

Theophyllin or Theocin was first isolated from the tea-leaf by Kossel, but in 
such minute quantities as not to be a commercial product until the discovery by 
Traube that it could be produced by synthesis resulted in its being put upon the 
market under the name of theocin. It is a crystalline substance, soluble in one 
hundred and seventy-nine parts of water at 18° C, in eighty-five parts at 37° C. 
It was first brought forward by Minkowski, as a very active diuretic, and has been 
reported upon by a number of German clinicians. According to C. Doering, it is 
about as poisonous as caffeine, but Doering, Thienger, and Kramer all agree that 
it is much more active as a diuretic than is either caffeine or theobromine, increas- 
ing remarkably both the excretion of water and solid matters from the kidney. 
It has been tried both in cardiac and renal dropsies and is found to be very positive 
in its influence. Not rarely theocin has produced disagreeable symptoms, the 
most common of which are those of gastric irritation; in some cases severe vomit- 
ing, headache, and general malaise have been reported; and Schlesinger in two 



DIURETICS 533 

oases noted the occurrence of epileptiform convulsions after the taking of five doses 
of 0.2 gramme of theooin. The effecl of theocin is also likely to be temporary, 
the system apparently in a short time becoming accustomed to its use, so that it 
fails to cause diuresis .* Its maximum effect is commonly apparent the second or 
third tlay of its ingestion. In order to avoid gastric irritation, it is better to give in 
frequent small doses up to 8 grains a day (0.5 Gm.). 

SALINE DIURETICS. 

Under this class are included those substances which increase the 
How of urine by altering the composition of the blood rather than 
by acting on the kidney itself. The present idea of their mode of 
action can be clearly comprehended only by some conception of the 
modern theory of the actions of salts and their ions. 

The Theory of Ions. — A neutral salt is a body resulting from 
the union of an electro-positive and an electro-negative element 
or radical. According to the ionic theory, when a salt is dissolved in 
water it exists in the solution not merely as a solution of the neutral 
body but is broken up at least in part, into its electro-positive and 
electro-negative components. This dissociation, as it is called, is 
not the same as the chemical separation of the molecule into its con- 
stituent elements, for the solution does not have the properties that 
a solution of these elements should have; thus, in a dilute solution of 
sodium chloride we have the positive ion sodium and the negative 
ion chlorine, but the solution does not show any chemical signs of 
the presence of free chlorine. The evidence for the occurrence of this 
dissociation is based upon the physical properties of the solutions of 
the salts; for instance, the boiling point of a saline solution is increased 
proportionately to the number of molecules dissolved in the solution, 
but we find that frequently the increase in the boiling point is dis- 
proportionately too great to be explained by the amount of salt 
dissolved, hence it is believed that the salt exists not only as a salt 
but also as its component ions, each of which acts as a molecule. 

Many bodies do not ionize at all; thus alcohol, C 2 H 5 OH, does not 
act as as a hydroxyl of ethyl, but acts as alcohol. Generally speaking 
radicals do not split into their component elements, but the radical 
itself exists as a distinct ion; for instance, sodium sulphate, Na 2 S0 4 , 
dissociates into two sodium ions and one S0 4 ion. Again, in the case 
of potassium ferrocyanide, K,Fe(CN) 6 , the ferrocyanide ion Fe(CN) 6 
remains intact, and the poisonous action of the cyanides is not 
developed. 

Salts generally do not completely ionize, so that the amount of 
dissociation which occurs will depend upon the character of the salt 
and the concentration of the solution; generally speaking the more 
dilute the solution, the greater is the dissociation. Therefore in 
considering the effects which will be produced by the introduction 

* Albanese believes that the rapid diminution of diuresis after the administration of theocin 
is due to the deposit in the renal canaliculi of crystals of trimethylxanthin; basing his belief upon 
microscopic studies, and upon the fact that he was enabled, by injecting large quantities of saline 
solution in the lower animals, to maintain the activity of the drug. 



534 LOCAL REMEDIES 

of a salt into the blood, we have to consider the action of the positive 
ion, of the negative ion, and of the salt itself; all of these factors 
are mutually concerned in what is known as the "salt action. " There 
are certain properties and certain effects upon the system which 
are -common to all crystallizable substances and are spoken of as 
"salt action." These effects are, to a large extent, connected with 
their influence on osmosis. 

In the case of many salts one of the other ions may be so toxic as 
to completely overwhelm the action of the other ion as well as the 
salt action, thus after the administration of strychnine nitrate, no 
effect can be perceived except the effect of the strychnine ion; and 
with potassium cyanide the cyanogen ion is so extremely powerful 
that the effects of the potassium ion are entirely masked and the action 
of the compound is indistinguishable from that of other salts of 
hydrocyanic acid. 

The effect of salt action as mentioned above, is due largely to a 
disturbance of the osmotic balance between the blood and the other 
tissues of the body. One of the results of this change is an increase 
in the flow of urine. This occurs because of the greater volume of 
the blood; for, if a concentrated solution of the salt is introduced into 
the blood stream, there is a passage of the water from the tissues of 
the body into the blood in order to reduce the solution of the salt to 
a concentration isotonic with the normal bodily fluids. If, on the 
other hand, a dilute solution of the salt is introduced into the circu- 
lation, a sufficient amount of water will be retained in the blood to 
maintain the isotonicity. It follows therefore that saline substances 
introduced into the circulation whether in concentrated or dilute 
solutions, tend to increase the volume of the blood and therefore 
to provoke diuresis. Theoretically, only the water and the foreign 
salt should be carried off in this diuresis, but, as a matter of fact, 
it has been observed that the kidney is apparently unable to separate 
completely the constituents which go to make up the urine and we 
find that the other solid matters are also increased; therefore, any 
crystallizable substance — such as sodium chloride, potassium acetate, 
sugar or urea — which is not too highly toxic to be introduced into the 
blood in sufficiently large quantities, will tend to provoke diuresis. 
But it is evident that, if equimolecular weights of two salts are intro- 
duced into the blood stream, the osmotic equilibrium will be most 
disturbed by the one which exists in the blood in smaller proportion, 
or is entirely foreign to it. Therefore the salts of potassium are more 
actively diuretic than the salts of sodium because there is a much 
larger quantity of sodium salts in the blood than of the potassium salts. 

POTASSIUM. 

As most of the mineral acid ions (except the chloride) are 
physiologically active, when the pure potassic effect is desired, the 
vegetable salts should always be given the preference. 



DIURETICS 536 

Potassium carbonate, the potash of commerce, is obtained from 
wood ashes and other sources. The crude carbonate occurs in the 
form of huge stony masses bu1 when purified so as to conform bo the 
V . S. Pharmacopoeia it is a white granular powder, very deliquescent, 

without odor and with a simply alkaline taste. It is soluble in less 
than its own weight of water but insoluble in alcohol. It is too 
irritant for general use as an internal remedy. 

Potassium bicarbonate, which because less irritant is much to be 
preferred therapeutically to the carbonate, is in the form of trans- 
parent colorless crystals, not deliquescent, slightly alkaline in reac- 
tion, soluble in about 3 parts of water, almost insoluble in alcohol. 

Potassium hydroxide is usually found in the form of white or 
nearly white semi-translucent pencils, very freely soluble in water 
and in alcohol. It is a very active caustic. It is rarely used internally 
anil then only in the form of the solution. 

Potassium citrate is found either in crystalline form, or as a white 
granular powder. It is deliquescent in air, freely soluble in water, 
sparingly so in alcohol. Its aqueous solution reddens litmus paper, 
but does not affect phenolphthalein. It is the least offensive to the 
palate of all the potassium salts except the tartrates. 

Potassium acetate, which occurs either in crystalline masses or as 
a white powder, is extremely deliquescent and soluble in less than 
half its weight of water, also freely soluble in alcohol. Its solution 
reacts alkaline to litmus, but does not affect phenolphthalein. 

Potassium bitartrate, or cream of tartar, differs from the other offi- 
cial salts of potassium in that it is practically insoluble in water, 
requiring 200 times its weight of water (77° F.) to dissolve it. It is 
acid in reaction, and has a pleasant acidulous taste. On account of 
the relatively large proportion of tartaric acid present it is an active 
hydragogue cathartic. (See p. 512.) 

Official Preparations : 

The following are the official preparations whose activity depends chiefly on 
the potassium ion. 

Potassii Acetas 15 to 30 grains (1-2 Gm.). 

Potassii Bicarbonas 15 to 30 grains (1-2 Gm.). 

Potassii Bitartras [Cream of Tartar] 15 to 45 grains (1-3 Gm.). 

Potassii Carbonas 5 to 10 grains (0.3-0.6 Gm.). 

Potassii Citras 15 to 30 grains (1-2 Gm.). 

Potassii Citras Effervescens (20 per cent).. . . 1 to 2 drachms (4-8 Gm.). 

Liquor Potassii Citratis (8 per cent.) i to 1 fluidounce (15-30 C.c). 

Potassii Hydroxidum [Caustic Potash] Not used internally. 

Liquor Potassii Hydroxidi (5 per cent.) 

[Liquor Potassse] 10 to 20 minims (0.6-1.2 C.c.) 

Physiological Action. — Local Action. — Potassium hydroxide, like 
other hydroxides, is a powerful escharotic, but many of its vege- 
table salts are more or less irritant. These salts are also powerful 
depressants probably of all of the higher tissues. 

The mineral salts of potassium appear to be excreted unchanged, 
whereas the salts formed with vegetable acids, as the acetate, or citrate 



536 LOCAL REMEDIES 

(except the bitartrate), are apparently oxidized in the body, being 
eliminated as carbonates. The great mass of the salt escapes 
through the kidneys but the studies of Kramer suggest that a small 
proportion is eliminated by the intestinal glands. 

Alfred S. Taylor, obtained from the urine of a patient who was taking two 
hundred and seventy grains of potassium nitrate daily, 158.7 grains per diem. 
Rsbuteau found that potassium chloride had no effect upon the acidity of urine, 
but that if the carbonate, acetate or citrate was taken the urine became alkaline. 
As the last two of these are neutral salts, it is evident that they are converted in 
the system into an alkaline salt, in all probability into a carbonate. 

N euro-muscular System. — Podocaepow believed that the action 
of salts of potassium in the frog is chiefly upon the muscles, but the 
experiments of Guttmann, of Ringer and Morshead, and of Ringer 
and Murrell, have definitely proven that the brain, the spinal cord, 
the motor and sensory nerve's, and the muscles are all attacked by 
potassium. According to Ringer and Murrell, the spinal cord and, 
next to it, the brain are the most sensitive to the action of the drug. 

Astalfoni found that when locally applied to the brain cortex, to the spinal 
cord, to the peripheral nerves, or to the muscles, the salts of potassium produce a 
very pronounced lessening of irritablity. When very weak solutions were employed 
this condition of depression was often preceded by one of excessive irritability, 
but when solutions of five per cent, were used, no such stage was observable. 

Circulation. — Although there is some evidence that in very small 
doses the potassium ion has a slight stimulant influence upon the 
heart, it is not yet proven. On the other hand, it is quite certain 
that, in full dose, potassium markedly lowers the arterial pressure, 
and in human medicine this is the only influence of the base upon the 
circulation which is clinically demonstrable. The fall of pressure is 
very largely due to the direct action of poison upon the heart, but 
there can be no doubt that the muscle-fibres of the blood-vessels 
are also depressed, so that the blood-pressure is reduced by the con- 
joint depression of the muscle-fibres of the heart and blood-vessels. 
This action is shown by Dogiel to be a portion of the wide-spread 
general muscular influence of the poison, the heart muscle and the 
arterial muscle-fibres being simply more sensitive to the influence of 
potassium than are the skeletal and intestinal muscles. The heart 
is usually arrested in diastole (Podocaepow and Guttmann), and as 
pointed out by Traube, its muscle may be unable to respond to 
electrical stimulation.* 

Traube asserts as the result of his experiments that, injected into the blood in 
doses of two or three grains, potassium nitrate produces a fall in the pulse-rate and 
a rise in the arterial pressure. Aubert and Dehn have experimented with a number 
of the salts of potassium, and found that, with the exception of the permanganate, 
they all act upon the circulation in the manner just described. It remains at present 
writing, however, doubtful whether the rise of pressure just spoken of is a direct 

* The poisonous influence of potassium upon the heart was, we believe, first discovered by 
Black (C. R. S. B., 1839), and has been abundantly confirmed. 



DIURETICS 537 

phenomenon caused l>y potassium. No dose of a potassium salt ever calls forth 
symptoms of circulatory stimulation from the human body. Further, Podocae- 
pow and also Aubert and Dehn affirm that the rise following the potassium injection 
in the animal usually lasts only three minutes, and that in no case is the maximum 
effect perceptible for more than ten minutes. Aubert and Dehn further assert thai 
there is no cumulative action, the repetition of small doses of the drug at brief 
intervals leaving no residual effect, the pressure returning to the normal after each 
injection, just'as though no previous injection had been given. The correctness of 
this statement remains doubtful, since Guttmann asserts that there is a gradual 

rise oi pressure. 

If there be a rise of pressure produced by the minute doses of potassium il 
would seem probable that it is due to an action upon the blood-vessel walls, since 
Molta/.i found it impossible by any dose to increase the vork done by the frog's 
heart; and in the experiments of Astalfoni, perfusion of minute doses of potassium 
through the blood-vessels of the kidney or of one exsected leg caused contraction 
of the arterioles. 

The method by which the changes in the pulse are produced by the small dose 
of potassium also remains uncertain. Traube affirms that if the vagi be cut after 
exhibition of potassium, the lessened pulse-rate instantly becomes rapid, and the 
already increased arterial pressure rises still further. The same observer also found 
that after section of the pneumogastrics small doses of the nitrate produced a fall 
in the pulse, with increased arterial pressure; but on a repetition of the dose in the 
same animal no lessening of the pulse-frequency was perceptible, while each time 
the pressure rose. This seems to indicate that the cardiac action of the drug is 
independent of the inhibitory apparatus, which is confirmed by the experiments 
of Aubert and Dehn upon atropinized clogs, and the work of Guttmann, who found 
that vagal section had no influence on the course of the poisoning. 

According to Aubert and Dehn, for a few seconds before complete suspension 
of cardiac movements there are irregular, "stormy" convulsions, winch run through 
the heart in a sort of peristaltic manner with great rapidity, but have no effect in 
expelling the blood. 

The observations of Aubert and Dehn, that the effect of potash is not per- 
manent indess it is continued a certain length of time, is in accord with that of 
Astalfoni, who foimd in using it locally that functional irritability could be restored 
by washing out the part with a weak solution of sodium phosphate. Podocaepow 
and Guttmann have found that in fatal poisoning the contractility of the cardiac 
muscle may be in a measure preserved if the potassium had been very slowly 
introduced into the circulation. 

Nutrition. — It seems to be clearly demonstrated that potassium 
increases the elimination of nitrogenous matter with the urine in 
both health and disease. It is well known that potassium increases 
oxidation outside of the body and its effect in hastening the kata- 
bolic changes appears to be dependent upon its oxidizing power. 

In an elaborate series of experiments upon himself, E. A. Parkes found that 
liquor potassae (two fluidrachms) when taken fasting, produced in from thirty to 
ninety minutes an increased flow of slightly acid urine containing the whole of the 
alkali and organic matter which differed in quality from that ordinarily found in 
urine, and was also larger in amount than normal. Golding Bird found in a dog, 
that three drachms of potassium acetate increased the uric acid about thirty-two 
per cent.; the urea, about sixty per cent.; extractives, including kreatine, kreati- 
nine, etc., about twenty per cent. Rabuteau found that the daily ingestion of 
seventy-five grains of potassium chloride caused an increase of twenty per cent, 
in the amount of urea discharged. Aug. Dehn has also experimentally found that 
the potassium salts greatly increase the elimination of urea. 



538 LOCAL REMEDIES 

The conclusion reached by experimental research made upon healthy men 
and animals — namely, increased tissue-cliange as the result of potassium ingestion 
— have been found to apply in disease. 

In six observations upon subjects affected with what may be termed indifferent 
diseases, such as lead palsy, Parkes found that the urea was increased, and also 
the sulphuric acid, by the use of drachm doses of liquor potassse. Austin Flint 
has studied the effect of potassium nitrate upon a number of persons suffering from 
various diseases, and found that, it very greatly increases the amount of solids 
in the urine. In rheumatism Parkes found that liquor potassae increased the elim- 
ination of sulphuric acid, but had no decided influence on the uric acid. He, 
however, used such small doses of the drug as not to get the effect obtained in 
the alkaline treatment of the disease, since he expressly states that the urine 
remained acid. 

Basham affirms, however, that, as the result of a series of analyses he lias found 
that in uric acid diathesis not only is there a great increase of the urea during the 
use of potassium, but also that the uric acid, either free or combined, in the urine 
is greatly diminished. Basham, remembering that Schunck had proved that, under 
the oxidizing power of potassium, uric acid outside of the body is converted into 
oxaluric acid, which in its turn is readily metamorphosed into oxalic acid and urea, 
carefully examined the urine of gouty patients taking the alkali, and found that 
not only was the urea increased, but that oxalic acid also appeared as the uric acid 
decreased, and that the urine, on standing, deposited crystals of calcium oxalate, 
although none of these could be found in it when first voided. This research of 
Basham certainly seems to demonstrate that in uric acid diathesis the potassium 
salt increases the oxidation and the ultimate metamorphosis of tissue. 

Therapeutics. — An important use of the vegetable salts of 
potassium is in acute inflammatory rheumatism. Before the intro- 
duction of the salicylates the alkaline treatment was the best that 
was known for cases of thoroughly acute rheumatism. This consists 
in the use of either the acetate or citrate of potassium with or with- 
out sodium or potassium bicarbonate. The medicine must be given 
freely, an ounce to an ounce and a half in the day, in sufficient dose 
to render and keep the urine alkaline. Opium may be at the same 
time employed in as large doses as are required to relieve the pain. 
After a few days, when the violence of the symptoms has abated and 
decided anemia appears, the exhibition of the drug should be dis- 
continued and potassium iodide, with tonics, be substituted. In cases 
subacute from the beginning a combination of the potassium iodide 
and acetate is sometimes very efficient, ten grains of the former and 
thirty of the latter being administered three or four times a day. 
The potassium probably does good in rheumatism by lowering arterial 
action, by favoring oxidation and elimination of partially effete 
materials, and by neutralizing excessive acidity. 

As depurants, the salts of potassium are very useful in various 
diseases. Attention has been especially called by Golding Bird to 
their value in that class of cases spoken of as chronic biliousness. 
In chronic malarial poisoning, in catarrhal jaundice, and in the jaun- 
dice of simple hepatic torpor they are often of use. In uric acid 
gravel and uric acid calculus the vegetable salts are useful in check- 
ing the deposition of the uric acid, but have no influence upon 
calculi already formed. 



DIURETICS 539 

The bitartrate appears to differ from the others Vegetable sails in 
being eliminated unchanged. An ounce (30 Gm.) of it in a pint of 
infusion of juniper-berries, taken, in divided doses, during the twenly- 
four hours, will very often act most happily in drops;/. In acute 
desquamative nephritis, potassium bitartrate is often very serviceable; 
as, however, the avoidance of irritation of the kidneys is imperative 
in this disease, the infusion of juniper should not he used. 

Administration. — As usually exhibited, the salts of potassium 
are exceedingly distasteful. There is no need of this whatever. The 
citrate dissolved in lemon-juice is entirely palatable. Still more 
pleasant is the effervescent potassium citrate of the U. S. Pharma- 
copoeia; this is, however, more distinctly laxative in its action on 
account of the sodium tartrate resulting from the reaction which 
causes the effervescence. 

Potassium Nitrate (Potassii Nitras), or Nitre, is ordinary salt- 
petre. It occurs in more or less perfect, long, striated, semi-trans- 
parent, six-sided prisms, with dihedral summits, or a white crystalline 
powder; of a sharp, saline, somewhat cooling taste; containing no 
water of crystallization, but decrepitating when thrown on the fire, 
from the evaporation of water mechanically retained in the cervices 
of the crystals; soluble in 3.6 times its weight of water, insoluble in 
absolute alcohol. 

Physiological Action. — Potassium nitrate is so violently irritant 
that the general effects of the potash in it upon the system are 
lost in the local symptoms caused by its overdose. It probably 
exercises a direct irritant action on the kidney as well as a salt action. 
On account of these properties it is vastly inferior to the vegetable 
salts of potassium, as a depurant, but is still occasionally used as 
a diuretic in cardiac dropsy. 

Toxicology. — The symptoms of poisoning by potassium nitrate 
are an intense burning pain in the stomach, coming on in a few min- 
utes after the ingestion of the poison, and soon followed by violent 
vomiting, and, it may be, free purging, with, after some hours, col- 
lapse, great muscular weakness, and not rarely local convulsive 
tremblings. The matters vomited, and even the stools, may be 
bloody (Husemann). Sometimes the nervous symptoms predominate, 
and the purging may be absent: collapse, with slight vomiting and 
with or without paralysis of the lower limbs, may alone exist. Sup- 
pression of urine has been noted in some cases.* After death, very 
grave lesions are found in the stomach and the intestines, such as 
intense redness and congestion, and effusion of blood into the sub- 
mucous coat, and sometimes into the stomach itself. Even ulcera- 
tion and corrosion of the mucous membrane have been observed. 
How far potassium nitrate acts upon the blood is at present uncer- 
tain; Mairet and Combemale assert that it alters the red blood- 

* Case, Pharmaceut. Journ., Feb. 1846, 356. 



540 LOCAL REMEDIES 

corpuscles. Sometimes, however, death has occurred, in poisoning 
by saltpetre, with great suddenness. In the only cases of this char- 
acter, the record of which we have read, the dose has been very large, 
and it is possible that the death has been the result of the paralyzing 
action of the potassium upon the heart. 

In the treatment of poisoning by saltpetre, after the stomach and 
bowels have been emptied, the usual means for the relief of toxic 
gastro-enteritis should be resorted to. 

Potassium Chlorate (Potassii Chloras) occurs in white rhom- 
boidal plates of a pearly lustre or a white granular powder, of an 
acerb taste, soluble in 16 parts of water, insoluble in alcohol. 

Official Preparations : 

Potassii Chloras 5 grains (0.3 Gm.). 

Trochisci Potassii Chloratis each 2\ grains (0.15 Gm.). 

Physiological Action. — Locally, this salt is irritant and astrin- 
gent. The physiological action of potassium chlorate is evidently 
dominated by the acid radical. S. J. Meltzer found that the injection 
of three to four minims of its five-per-cent. solution produced imme- 
diate violent convulsive disturbances, with coma, and that similar 
symptoms were caused by the sodium chlorate, and it is evident that 
both salts act directly upon the nerve-cells. 

The theory that potassium chlorate yields its oxygen in the system 
is absurdly untrue.* The potassium chlorate escapes unchanged 
chiefly with the urine, but also in the saliva, and probably all the 
secretions of the body. 

Isambert found it in the tears, the bile, the nasal mucus, and even in the milk 
of nursing women. Rabuteau, Isambert and J. von Mering have each recovered 
from ninety to ninety-nine per cent, of the ingested salt from the urine. Indeed, 
Marchand, in experiments upon the lower animals, asserts that he has recovered all 
of the ingested chlorate from the secretions, and we must conclude tliat it practically 
all escapes from the body unchanged. 

Von Mering in one or two instances in the dog found a slight increase in the 
chlorides of the urine during the administration of the chlorate, and it is possible 
that a minute quantity of the chlorate does undergo deoxidation; but it must be 
considered established that any such change, if it occurs at all, affects so small a 
portion of the drug as not to be worthy of consideration. 

The therapeutic 'dose of potassium chlorate produces no sensible 
effects in the system. Isambert found that, when taken by himself 
in doses of from two to five drachms, it caused salivation, free diuresis, 
increase of the appetite, and, when not well diluted, gastric irritation; 
the urine continued strongly acid, and contained an excess of rosacic 
acid, uric acid, and the urates. 

Therapeutics. — There is no systemic effect of potassium 
chlorate which justifies its use as an internal remedy. On account 
of its strongly irritant effects on the kidneys it should never be used 



* For detailed discussion, see tenth edition. 



DIURETICS 541 

for its salt action as a diuretic The only use for which it is suitable 
is as a local stimulant in inflammations of mucous membranes, 
especially of the mouth. In the follicular or aphthous stomatitis of 
children * it is almost a specific. In ordinary sore throat or angina 
a solution containing three to four per cent, of potassium chlorate 
with fifteen to twenty-five per cent, of the fluidextract of rhus glabra 
is. as a gargle, most effective. 

In chronic dysentery and other diseases of the colon it may be 
applied by means of the large enemata. In hemorrhoids the injection, 
when the patient goes to bed, of half to one ounce of its saturated 
solution, combined with a few drops of laudanum to secure retention, 
is often of the utmost service. In stomatitis it is best employed in the 
form of the troche. 

Toxicology.— As a poison it has frequently caused death. f 
The smallest fatal dose is not known, but half an ounce has killed. 
A drachm taken during a night has killed an infant a year old, and 
three drachms a child three to four years old. The symptoms may 
be acute or subacute. In the rapid cases there have been violent 
vomiting, profuse diarrhoea, excessive dyspnoea, great failure of the 
heart's action, and marked cyanosis. In the subacute cases the 
gastro-intestinal symptoms have been severe, with generally vomit- 
ing of blackish-green matters and distinct swelling of the liver and 
the spleen. The urine is markedly lessened in quantity, albuminous, 
often of an opaque reddish-brown or blackish color, and showing 
under the microscope brownish or yellowish-brown tube-casts, fre- 
quently containing the detritus of blood-corpuscles. Hemoglobinuria 
has been noticed,! and methemoglobin is a common symptom. The 
nervous symptoms have been severe delirium, coma, tonic and clonic 
cramps, and a peculiar stiffness of the extremities. 

Headache, loss of appetite, violent pains in the abdomen and 
other portions of the body, and marked abdominal tenderness have 
usually preceded the loss of consciousness. Not rarely there are 
minute ecchymoses upon the surface of the body, and even more 
frequently there is a general jaundice. In some cases the patient 
has rallied and seemed to be on the road to recovery when the fatal 
relapse has occurred. 

After death the blood is usually chocolate-colored, the gastro- 
intestinal tract is inflamed, the liver and spleen are enlarged and 
filled with the brownish debris of red blood-corpuscles, the bone- 
marrow and the brain are often similarly colored, while the mucous 
membranes are usually swollen and ecchymosed. The kidneys are 
profoundly affected, their tubules full of brownish casts and their 
epithelial structure evincing a nephritis. The most characteristic 



* Laborde (Ball. 77ie>ap., 1874, Ixxxvii.) and Tacke (Inaug. Diss., Bonn, 1878) have shown 
that sodium chlorate acts physiologically like the potassium salt; and S. Ringer and H. Sainsbury 
[London Lancet, 1882, ii. 736) have found it equally efficient in stomatitis. 

t For collection of cases, see Chlorsaure Kali, J. von Mering, Berlin, 1885. To Jacobi, of New 
York, belongs the credit of having first called attention to the dangerous action of this much- 
abused remedy (Amer. Med. Times, April, 1861, 245). 

t Trans, internal. Congress, 1881, I. 463. 



542 LOCAL REMEDIES 

and probably the most important of (lie lesions is the change in the 
blood, which was first noticed after death by F. Marchand. L. Riess 
noted in a case during life that many of the red blood-corpuscles 
were decolorized, and others contained little granules of an elliptic 
shape. The changes in the blood are the result of the formation of 
a substance apparently identical with the methemoglobin of Hoppe- 
Seyler and characterized by the appearance in its spectrum of a 
dark line in the red. Methemoglobin is readily produced by mixing 
either sodium chlorate or potassium chlorate with blood: that it is 
produced in the body during life has been experimentally proved 
in cats, dogs, and rabbits by A. Falck, by H. Lenhartz, and by 
Cahn, and is also shown in man by the wide-spread staining not 
only of the interior of the blood-vessels, but also of the walls of the 
whole lymphatic system, found after death from the chlorate. (Case, 
N. Hammer.) 

LITHIUM. 

Lithium is used as a base for the carrying of a number of active 
acids, as benzoic, salicylic or hydrobromic, but the pharmacopoeia 
recognizes two salts, the carbonate and the citrate, whose usefulness 
depends upon the lithium ion. 

Lithium carbonate is a white odorless powder with a somewhat 
alkaline taste and only sparingly soluble in water. 

Lithium citrate occurs as a deliquescent white powder, or in 
colorless crystals. It is soluble in twice its weight of water. 

Official Preparations : 

Lithii Carbonas 10 to 30 grains (0.6-1 Gm.). 

Lithii Citras 10 to 30 grains (0.6-1 Gm.). 

Lithii Citras Effervescens (5 per cent.) 2 to 4 drachms (8-15 Gm.). 

When one of the official salts of lithium is ingested absorption 
begins almost immediately. The lithium has been detected in the 
urine by Clarence Good ten minutes after the hypodermic injection. 
Excretion goes on, however, slowly, since the same chemist has found 
lithium in the urine twenty-three days after the injections had been 
stopped. The chief channel of escape is through the urine, but excre- 
tion occurs also from the salivary and gastro-intestinal glands. No 
cases of serious poisoning by a lithium salt have been recorded, but 
we have seen large, repeated doses produce pronounced malaise, with 
muscular weakness and some disorder of the digestion. According to 
P. Pergami the exhibition of lithium carbonate distinctly increases 
the alkalinity of the blood. 

According to the studies of Binet, the lithium salts produce in 
mammals pronounced feebleness, with nausea, diarrhoea, and other 
digestive disturbance, increasing dyspnoea, fall of temperature, and 
death, usually preceded by convulsions. Death is said to be due to a 
direct centric arrest of respiration, although a markedly depressing 
influence is exerted upon the heart, which is finally arrested in diastole. 



DIURETICS 543 

When life is maintained by artificial respiration the peripheral nerves 
become entirely paralyzed and the muscles affected, as is shown 
by peculiar fibrillary contractions. In poisoned frogs, also, the 
excitability of the muscles is somewhat diminished. 

Lithium salts were originally recommended by Ure and Garrod 
in the treatment of uric acid diathesis and of chronic gout; theoreti- 
cally because it was believed they had the power of dissolving uric 
acid and the urates. As the dissolving action is, however, only 
manifest in quantities too great for therapeutic administration and 
as uric acid, according to modern pathological ideas, plays only a 
very secondary role in gout or rheumatism it is evident that the value 
of lithium is slight. It probably exercises some depurant effect 
similar, but greatly inferior, to potassium. E. Duche affirms that 
their prolonged local application is very useful in relieving gouty 
joints, ami that in gouty conjunctivitis frequent washing of the eye 
with a solution of lithium carbonate, 1 to 500, is effective.* 

Piperazin. — Piperazidine, or Diethylendiamine, occurs in small, 
glassy, lustrous tables, or, in the form of the hydrochlorate, in silky, 
lustrous, lanceolate crystals. 

Because of the fact that uric acid is soluble in solutions of piper- 
azin, while the theory that uric acid as the causative factor in remov- 
ing conditions was still prevalent it was a remedy which enjoyed 
a considerable popularity in the treatment of various gouty and 
rheumatic diseases. It has not, however, proven itself a remedy of 
great practical value. It may, perhaps, be of some service in cases 
of uric acid gravel. 

Piperazine is rapidly absorbed and eliminated through the kid- 
neys, producing a reddish-brown urine. Concerning its general 
physiological action there is very little knowledge. The therapeutic 
dose produces in man ordinarily no symptoms, but we have seen 
muscular weakness and general depression follow the continuous exhi- 
bition of large doses. Whether it does or does not affect the general 
nutrition is unknown. Vogt asserts that it checks uric acid elimina- 
tion. Ebstein and Sprague have found that it has no effect either upon 
the excretion of urea or of uric acid. It has been very largely used in 
gout, but has failed to sustain its first reputation, although in occa- 
sional cases it apparently exerts a markedly beneficial influence for 
a time. It causes too much pain to be used hypodermically; fifteen 
to twenty grains (1-1.3 Gm.) of it may be administered by the mouth, 
during the day, in a quart of plain or carbonated water. It is too 
hygroscopic and too easily decomposed to be given in powder or in 
watery solution, but the solution of one part in twenty of alcohol 
and eighty of water is said to be fairly permanent. Van der Klip 

* Martineau's Solution. — Martineau affirms that he has obtained very remarkable results 
in the treatment of diabetes mellitus by the use of a solution of lithium carbonate and sodium arsen- 
ate. In gouty diabetes this arsenical solution of lithium may prove of service: from five to ten 
grains of lithium carbonate and one-thirtieth of a grain of sodium arsenate may be given three times 
a day. 



544 LOCAL REMEDIES 

has found that in the lower animals, in sufficient dose, it produces 
vomiting, irregular breathing, general muscular weakness, and relax- 
ation; that it decreases the oxidizing power of oxyhemoglobin and 
the coagulability of the blood; and that it checks the action of 
peptonizing ferments.* 

Sugar. — Various sugars, when taken in sufficient quantity to 
exercise a "salt action, " are capable of provoking diuresis. Although 
not frequently used for this purpose it has been affirmed by S. Meslach, 
Zavadsky, Germain-See, and other clinicians that both glucose and 
the sugar of milk may often advantageously be used in the treatment 
of cardiac dropsy, pleuritic effusions, etc., but are of little value when 
there is renal disease. The general testimony seems to be that the 
sugar of milk is the more active of the two. These sugars may be 
given in doses of from one to six ounces (30-180 Gm.) a day, admin- 
istered in concentrated syrup or in milk. According to the experi- 
ments of Albertoni, all sugars injected into the veins cause a rise of 
the arterial pressure by a direct stimulation of the heart. He also 
found that the kidneys, as tested by Roy's oncometer, become 
congested or swollen. 

Official Preparations : 

Saccharum — Cane Sugar. 
Saccharum Lactis — Milk Sugar. 
Syrupus (85 per cent.) 

STRONTIUM. 

The only official salts of strontium are the bromide, iodide and 
salicylate which are described under the head of their respective 
acids. The effects of the strontium ion are here considered. 

Absorption and Elimination. — Our present knowledge indicates 
that the soluble salts of strontium are precipitated by the alkalies 
and phosphates of the intestines, so that they are only partially ab- 
sorbed; and that elimination is even more slow than absorption; 
so that strontium has a tendency to accumulate in the liver, in the 
muscles, and especially in the bones. 

Horatio C. Wood, Jr., (confirmed by H. C. Wood and John P. Arnold) deter- 
mined that when an official salt is administered by the mouth only a minute propor- 
tion of it can be obtained from the urine, while a great amount is readily obtainable 
from the feces. It was further found that when it has been given hypoder- 
mically only a minute proportion of strontium escapes with the urine. The research 
of L. R. Mendel and H. C. Thacher indicates, however, that more of the strontium 
is absorbed than would seem to be indicated by the results of the earlier investi- 
gators. These researches confirmed the results previously obtained, but showed 
further that when strontium is subcutaneously or intravenously given, a large por- 
tion of it can be obtained from the feces, so that elimination must take place in the 
alimentary canal. It is, however, probable that the strontium found in the feces 

* H. Hildebrandt {Berlin. Klin. Wochen., 1894) having found that piperazine, even in small 
quantities, checks the saccharifying influence of hemic and other hydrolytic ferments, although it 
has no destroying influence, tried the drug in diabetes produced in dogs by phloridzin with 
pronounced success; so that the remedy is certainly worthy of trial in diabetes mellitus. 



DIURETICS 



545 



after the administration of the drug by the mouth represents not only, as believed 
by Mendel and Thacher, strontium which has been absorbed, but also even more 
largely strontium which has failed of absorption.* 

Physiological Action. — Binet affirms that the continuous 
use in the lower animals of excessive doses of strontium produces 
general feebleness with increasing dyspnoea, cyanosis, clonic convul- 
sions, and death from asphyxia. When recovery occurs the motor 
power gradually returns, with stiffness, ataxic movements, and not 
rarely with the assumption of bizarre positions. 

As was shown by Wood and Arnold, when injected into the blood- 
stream, the salts of strontium produce a marked slowing of the pulse- 
rate with a notable increase in the arterial pressure. If the dose is 
sufficiently large the pulse later becomes rapid and the arterial press- 
ure falls somewhat, although it may not reach the normal. After 
toxic doses, however, both the pulse-rate and the pressure at last 
gradually fall to zero. The rise in pressure is due to the conjoined 
stimulation of the cardiac muscle and also a direct stimulation of 
the arterial walls. These authors confirm the conclusions of Lauder 
Brunt on, that strontium affects directly the voluntary muscles pro- 
ducing a primary increase of muscular power with a final paralysis. 
Evidently strontium is a muscle-poison which first stimulates and 
afterwards paralyzes the muscle-fibres, acting both upon the muscles 
of the skeleton and upon those connected with circulation; its stimu- 
lating effect upon the circulation being, therefore, the result of a 
wide-spread general influence of the drug upon the muscle-fibres 
both of voluntary and involuntary life. It is probable, though not 
proved, that the muscle-fibres in the intestines are also affected by 
the strontium salt. 

According to Binet, in poisoning by strontium, the nerve-centres 
are more powerfully affected by the drug than are the muscle-fibres 
themselves, death occurring in the frog from centric respiratory 
paralysis; the peripheral nerves and the muscles, although depressed, 
still retaining after death some functional power. 

Strontii Lactas. — Strontium Lactate occurs as a white granular powder, or 
in crystalline nodules. It is odorless, of a slightly bitter saline taste, permanent 
in the air, and soluble in about four parts of water; also soluble in alcohol. Accord- 
ing to Germain-See, Paul, Dujardin-Beaumetz, and other French clinicians, it is a 
valuable remedy in the treatment of chronic Bright's disease, increasing the amount 
of urine, diminishing or arresting the excretion of albumin, and improving the gen- 
eral nutrition. In albuminuria due to pulmonary congestion the drug is said to be 
of service, and it is further affirmed that its influence for good is especially marked 
in desqwimative nephritis and much less pronounced in interstitial nephritis. In 
many cases there is no increase in the flow of urine, and the good achieved seems 
to be due to an alterative influence upon the secreting structure of the kidney. In 
our own experience the strontium lactate has not yielded results such as are ascribed 



* The presence of strontium phosphate in bone-ash is affirmed by some and denied by other 
chemists. According to the experiments of Max Cremer, the feeding of strontium phosphate to 
young hounds has no influence in preventing the development of rickets (Milnchen. Med. V/ochen., 
1892). 



35 



546 LOCAL REMEDIES 

to it by the French observers. It is, however, a harmless remedy, whose use should 
not prevent the administration of other appropriate drugs. The usual dose is from 
twenty to thirty grains (1.3-2 Gm.), given three times a day in solution; but much 
larger amounts liave been exhibited without producing apparent symptoms. 

ALTERATIVE DIURETICS. 

Under the term of alterative diuretics are included a number of 
drugs which are used chiefly for their effect upon the mucous mem- 
branes of the urinary tract. Most of these substances contain prin- 
ciples which are more or less antiseptic in their action. Many of 
them, however, unite to this antiseptic action, a local stimulant 
effect, which makes them useful especially in chronic inflammations. 
Those of the alterative diuretics such as turpentine and juniper, 
which contain irritant principles, will in a healthy kidney increase 
the secretory activity, but their use for this purpose is comparatiA-ely 
infrequent. 

BUCHU. 

The leaves of Barosma betulina, a native of Southern Africa. 
These leaves are an inch or less in length, from three to five lines 
broad, of various forms, but always notched on the edges, and hav- 
ing a strong, rather rank, yet somewhat aromatic odor, and a warm, 
bitterish taste. They owe their virtues, which they yield to water 
and to alcohol, to a volatile oil and a bitter extractive. 

Fluidextractum Buchu 1 fluidrachm (4 C.c). 

Therapeutics. — Buchu is a mild stimulant and alterative to 
the mucous membrane of the genito-urinary organs, useful in sub- 
acute and chronic cystitis, chronic pyelitis, and irritation of the bladder. 
Its oil is undoubtedly absorbed, and is eliminated by the kidneys, 
to whose secretion it imparts its odor. In irritated bladder, when the 
urine is highly acid, and when there is a constant desire to urinate, 
with but little relief from micturition, buchu, in combination with a 
vegetable salt of potassium and the sweet spirit of nitre, often gives 
great relief. 

UVA URSI. 

Bearberry is the leaves of Arctostaphylos Uva-ursi, a low ever- 
green shrub, indigenous to northern maritime Europe, and also to 
our northern coasts as far south as New Jersey. They are from half 
an inch to an inch in length, wedge-shaped, thick, coriaceous, with 
a smooth, rounded margin. The odor is hay-like, the taste bitterish, 
astringent, and somewhat sweetish. The most important constit- 
uent of uva ursi is the glucoside arbutin, which occurs in long acicular 
colorless crystals, freely soluble in water, less so in alcohol and in 
ether, and is resolved by the action of sulphuric acid into glucose 
and hydrochinone. 

Fluidextractum Uvae Ursi 2 to 4 fiuidrachms (8-15 C.c). 



DIURETICS .'.17 

Therapeutics. — Uva ursi lias been long used in medicine for 
its influence upon the genito-urinary mucous membrane, and a) 
present is employed only in chronic pyelitis, cystitis, and other affec- 
tions of the genito-urinary mucous membrane, when a slightly stimu- 
lant and an astringent action is desired. Hughes found that in doses 
of one grain arbutin is a powerful diuretic. It seems to be free from 
poisonous properties, as Jablonowski took in forty-eight hours eigh- 
teen grammes of it without discomfort. It produces a discoloration 
of the urine varying from pale greenish to dark greenish brown, the 
color deepening upon standing due, as has been shown by Yon Mering, 
by L. Lewin, and by Steffen to the formation of hydrochinone. The 
change probably occurs in the kidneys, as arbutin is free from toxic 
properties, while Brieger has shown that hydrochinone is poisonous. 
The experiments of Forster show that hydrochinone * is a powerful 
disinfectant and antiferment. It is stated that a one-per-cent, solu- 
tion will arrest putrefaction and alcoholic fermentation, while one-half 
per cent . is sufficient to check butyric fermentation. Concerning 
the therapeutic value of arbutin there has been much discussion, 
but the fact that it has failed to come into general use indicates that 
it has little practical effect, and that H. Laurentz was right in assert- 
ing that uva ursi is of value in genito-urinary diseases chiefly on 
account of its tannic acid and of the volatile oil which it contains. 

Pareira. — Pareira Brava is the root of Chondrodendron tomen- 
tosum, a climbing plant of South America. There appear to be in 
the root one or more alkaloids. f Pareira Brava has been used with 
asserted advantage in cystitis, in irritable bladder, and in chronic 
i/onorrha'a, and appears to exert a stimulant action upon the mucous 
membrane of the whole genito-urinary apparatus. 

Fluidextractum Pareine 1 fluidrachm (4 C.c). 

Chimaphila. — Pipsissewa is the dried leaves of Chimaphila 
umbellata, a little indigenous perennial, distinguished from its inert 
congener C. maculata by the uniform glossy green of its leaves. It 
contains tannic acid, bitter extractive, and, according to Samuel 
Fairbank, a crystalline principle, chimaphilin. Pipsissewa is nearly 
equivalent to uva ursi in its therapeutic value, though not so effective. 

* According to the experiments of Brieger, hydrochinone produces in man giddiness, ringing 
in the ears, and lessening in the force and frequency of the pulse. In the experiments of P. J. 
Martin (Therap. Gaz., 1887, 289), it caused in the frog violent convulsions, followed by paralysis 
anil death through failure of the respiration, both convulsions and paralysis being the result of a 
direct influence upon the spinal cord. Small doses in the mammal produced stimulation of the 
vaso-motor centres, this, if the dose were sufficient, was followed by a depression. The bodily 
temperature was lowered by large doses from an increase of heat-dissipation, probably the result 
of a vaso-motor paralysis. II. G. Beyer, after experimenting upon the frog and terrapin (Amer. 
Journ. Med. Sci., April, 1886), came to the conclusion that hydrochinone affects both the heart 
and the vessels as a paralyzant, lessening the rate of the heart and the amount of work done, and 
causing dilatation of the arterioles. Antaeff has found that if two per cent, of hydrochinone be 
added to fresh urine the latter will remain for many days without undergoing alkaline fermentation, 
but that if hydrochinone be added to a solution of urea a rapid decomposition of the urea occurs, 
which Antaeff believes to be the result of a direct chemical action of hydrochinone on urea (Lancet, 
April, 1887). 

t See V . S. Dispensatory, 19th ed. 



548 LOCAL REMEDIES 

Fluidextractum Chimaphilae 1 fluidrachm (4 C.c). 

Triticum. — The rhizome of Agropyron repens or couch-grass 
of Europe and the United States, is believed by many surgeons to 
have a sedative influence upon the genito-urinary organs, and has 
been considerably used in irritable bladder and cystitis. 

Fluidextractum Tritici 2 fluidrachms (8 C.c). 

TURPENTINE. 

The United States Pharmacopoeia recognizes under the title 
turpentine (Terebinthina) the concrete oleoresin obtained by incising 
Pinus palustris and other species of pine; and under the title of 
Canada Turpentine (Terebinthina Canadensis), the liquid oleoresin 
commonly known as Canada balsam which is the product of Abies 
balsamea, or American Silver Fir, a beautiful evergreen indigenous 
to the extreme Northern United States and to the British provinces. 
It is a thick and viscid but clear, yellowish liquid, which by age and 
exposure becomes converted into a hard, brittle, translucent, resinous 
mass. Canada Balsam is very rarely, if ever, used in medicine, but 
resembles turpentine in its action on the system: when fresh it con- 
tains about twenty per cent, of the volatile oil, which is its active 
ingredient. 

Turpentine, or, as it is sometimes called, White Turpentine occurs 
in yellowish opaque brittle masses practically insoluble in water but 
completely soluble in alcohol. It is rarely, if ever, itself used in 
medicine, but by distillation is separated into a volatile oil and a 
resin (Rosin), which is official under the name of Resina. 

The oil of turpentine is a yellowish, highly inflammable oil, of a 
strong peculiar odor and a hot biting taste, moderately soluble in 
alcohol, freely so in ether, very slightly so in water. By heating with 
hydrochloric acid it is converted into a red liquid and a white crystal- 
line substance, which, from its resemblance to camphor, has received 
the name of artificial camphor. Turpentine oil is remarkable for 
having the property of absorbing oxygen and converting it into ozone.* 

Official Preparations: 

The official preparations containing the oil of turpentine are: 

Oleum Terebinthinae Not used internally. 

Oleum Terebinthinae Rectificatum 5 to 15 minims (0.3-1.0 C.c). 

Emulsum Olei Terebinthinae (15 per cent.). . . 1 fluidrachm (4 C.c). 
Linimentum Terebinthinae (35 per cent.) . . . .External use only. 

The following are the preparations of rosin: 

Ceratum Resinae [Basilicon Ointment] External use only. 

Ceratum Resinae Compositum External use only. 

Ceratum Cantharidis External use only. -- 

Linimentum Terebinthinae External use only. 

* For a study of the effect of the ozonizing turpentine oils, see Pallop (Dorpat Thesis, 1889). 



DIURETICS 549 

Physiological Action. — Locally, oil of turpentine is a power- 
ful irritant, causing in a very short time inflammation in any tissue 
with which it comes in contact. It has been asserted that oil of 
turpentine is a powerful bactericide; but the experiments of Koch 
and of Christ mas- Direkinck-Holmfeld appear to show that its general 
antiseptic properties are feeble. It appears, however, to be especially 
antagonistic to the Bacillus typhosus. 

When taken by a healthy person, in moderate doses, it produces a 
sense of warmth in the stomach, soon followed by exhilaration, and, 
if the amount be sufficient, giddiness and even a species of intoxi- 
cation. The pulse is increased in force and frequency. The turpen- 
tine escapes from the body through the lungs and kidneys, imparting 
its own odor to the breath and that of violets to the urine. 

Circulation. — The investigations concerning the systemic effects 
of oil of turpentine indicate that the European oil differs markedly 
in its properties from that of the American markets. The turpentine 
oil of Europe appears to be a stimulant to the medulla, especially 
the vaso-motor and cardio-inhibitory centres. On the other hand, 
the American variety has little action on the circulation unless given 
in very large dose, in which case, it is depressant to the heart. 

R. Kobert, using the European turpentine, found that in moderate doses it 
exerted a powerful stimulating influence upon the inhibitory reflex centre, and also 
elevated the blood-pressure by stimulating the vaso-motor centres. Very large 
doses appeared to paralyze both of the centres spoken of, causing decided fall in 
the arterial pressure. The respiration was first increased in frequency, but later 
very much diminished. The blood became very dark, and the heart was finally 
paralyzed. It is said that these results are in accord with those previously pub- 
lished by Azary in the Hungarian language, and Hoppe concludes as the result of 
his own experiments, presumably made with European oil of turpentine, that the 
vaso-motor nerves are very early influenced by the drug. 

On the other hand, in a series of experiments made in the laboratory of the 
University of Pennsylvania by H. A. Hare with American oil of turpentine, it was 
found impossible to produce any marked rise in the arterial pressure. Large doses 
produced a pronounced fall of arterial pressure, with great cardiac depression, to 
which, indeed, Hare attributes the fall of the blood-pressure. Doses which had 
no effect on the blood-pressure increased the frequency of the pulse by an action 
upon the heart itself. When large doses w T ere administered the pulse became 
slow, — probably, as Hare believes, as the result of stimulation of the pneumo- 
gastric nerves, since section of these nerves was followed by the normal rise in 
pulse-frequency. 

Nervous System. — F. Fleischmann found that two drops pro- 
duced paralysis in the frog, — first of voluntary and afterwards of 
reflex activity; in the cat and in the rabbit, toxic doses abolished 
reflex activity, but caused violent lethal convulsions. The preserva- 
tion of voluntary movement in the frog after the loss of reflex activity, 
which has been confirmed by Hare, indicates that toxic doses of tur- 
pentine paralyze the sensory nervous system, either in the cord or in 
the peripheral nerves. 

Kidneys. — The irritant action of turpentine upon the kidneys and 
genito-urinary tract is very decided. "\Jhen moderate doses (ten 



550 LOCAL REMEDIES 

minims every three hours) of turpentine are taken, there are usually 
no renal symptoms produced, except a slight increase of the urine. 
Somewhat larger amounts, when exhibited, are likely to give rise to 
aching in the loins and to frequent micturition, with perhaps urethral 
pain accompanying the act. If still larger quantities are ingested, 
these symptoms are intensified, and at the same time the secre- 
tion of urine is diminished. After very large repeated doses of the 
drug, the aching in the loins is very great, often with spasmodic pain 
in the ureters; a constant desire to pass water struggles with the 
inability to micturate, caused by the urethral spasm; the urine is 
very scanty, albuminous, and even bloody; priapism may be present, 
and an intolerable irritation may affect all the pelvic organs. 

Therapeutics. — Externally the oil of turpentine is very much 
employed as a powerful counter-irritant. It is useful more especially 
when it is desired to act upon a large extent of surface. When a very 
intense permanent local impression is required, a blister is to be 
preferred. Thus, in -pleurisy a blister may be used, in bronchitis, 
turpentine stupes. In preparing the latter the turpentine should 
-' first be warmed by setting the vessel containing it in hot water, then 
a piece of flannel, just previously saturated with hot water and 
wrung out as dry as possible, should be dipped in the turpentine 
and again wrung out. It is then ready for application, and may be 
left on from fifteen minutes to half an hour, according to the sensi- 
tiveness of the skin. For milder effects it may be advantageously 
applied in the form of the liniment. 

Another local use of the oil of turpentine is as an addition to 
enemata. From a teaspoonful to a tablespoonful of it mixed with 
double its amount of olive oil renders opening enemata much more 
active, especially in causing the expulsion of flatus. Turpentine 
enemata containing much of the oil in a small bulk are also constantly 
used with good effect in arousing the system from stupor arising 
from narcotic poison or similar causes. 

In ulceration of the bowels turpentine taken by the stomach is often 
very efficient, probably acting locally in the intestine, and in old 
gastric ulcers good results are sometimes derived from its use. In 
a single large dose (one-half to one fluidounce, with an equal amount 
of castor oil) it is an efficient vermifuge. It may also be used as a 
stimulant in low fevers, particularly when the tongue is dry and red. 

In typhoid or enteric fever it without doubt acts as a local stimu- 
lant to the ulcerated bowel, besides influencing the general condition 
of the system. There are two conditions or stages in the diseases 
named in which it is especially useful, — indeed, is of incalculable 
service. About the end of the second week the tongue sometimes 
becomes very dry, red, chapped, perhaps coated in the centre with a 
brownish fur, and at the same time marked meteorism develops. 
Ten minims (0.6 C.c.) of turpentine every two hours during the day 
and every three hours during the night will in the majority of cases 
remove the bad symptoms noted. That the action of the oil is largely 



DIURETICS 551 

a local one is shown not only by the arguments of the introduce!- of 
the practice, George B. Wood, but also by the value of the same 
treatment when diarrhoea persists after the acute stage, of the fever 
has passed. When convalescence LS protracted, when there is a con- 
stant tendency to the recurrence of diarrhoea, — when, in other words, 
the ulcers of l'eyer's patches are slow to heal, — turpentine acts almost { 
as a .specific. These clinical results have received scientific confirma- 
tion in the work of Theo. Omclchenko, who finds that the bacillus 
of typhoid fever will not develop in air containing diluted vapor of 
turpentine, and dies when the atmosphere is saturated with the 
vapor. Thymol appears to be even more active than is turpentine. 

In typhoid bronchitis and pneumonia, especially as intercurrent ■*, 
in typhus fever and similar diseases, turpentine applied externally 
and taken internally is often very useful. The same may be said of 
i he low forms of puerperal fever. In this disease the abdomen should 
be kept covered with fomentations of the oil and of warm water 
alternately, the counter-irritant being used as constantly as a proper 
regard for the skin of the patient will allow. Internally it should be 
given in very large doses (ten to fifteen minims (0.6-1.0 C.c.) every 
two hours). 

In hemorrhages from the stomach, bowels, or lungs, turpentine 
has acquired celebrity, but it is hardly so much used as formerly. 
It is in the ataxic cases that it is useful. We have very rarely 
employed it. In purpura Juvmorrhagica turpentine has been highly 
praised.* 

Oil of turpentine is never employed to increase the flow of urine 
for the purpose of affecting serous effusions. As a diuretic, it is used 
solely for its local influence upon the organs. Excessive diuresis 
sometimes is apparently dependent upon a relaxed condition of the 
kidneys, and under these circumstances oil of turpentine may be of 
service. Chronic pyelitis, chronic cystitis, and gleet may be benefited 
by its use. 

In giving turpentine in these cases, it should always be borne in 
mind that, with the exception of cantharides, it is the most actively 
stimulating of all the diuretics, and must be employed only when 
such a remedy is called for. In those comparatively rare cases of 
urinary incontinence which are dependent upon debility of the 
bladder, turpentine is sometimes of great service. When the same 
symptom is spasmodic, the remedy, of course, is harmful. In 
absolutely passive hematuria, in impotence, in certain conditions of 
spermatorrhoea, and in amenorrhea, when great local debility exists, 
turpentine may be tried with fair hopes of its being useful. 

Toxicology. — Although several recorded instances prove that 
turpentine is capable of producing death, cases of serious poisoning 
by it are rare, and a lethal result is exceedingly so. The symptoms 

* I-con Cruris has made some experiments which indicate that when turpentine is given in 
toxic doses to rabbits it increases the coagulability of the blood and gives rise to numerous minute 
hepatic and pulmonic thrombi. 



552 LOCAL REMEDIES 

noted in poisoning by it are most of them constant, but vomiting 
and purging are present in some cases and not in others. Uncon- 
sciousness is generally complete, and occasionally is accompanied 
by dilated pupils; the urine is very much lessened in quantity, often 
bloody, not rarely suppressed; the skin is sometimes dry, sometimes 
moist; the pulse is feeble, rapid, and generally regular. 

The lethal dose must be very large, but it is not definitely known, 
since recovery from four ounces in an infant fourteen months old 
has been reported. In Maund's case, death was supposed to have 
been produced in an intemperate woman by six ounces; and Philip 
Miall has recorded an instance of death caused in an infant fourteen 
weeks old by turpentine, of which half an ounce was thought to have 
been taken 

COPAIBA. 

This oleoresin obtained from Copaiba Langsdorffii and other 
species of Copaiba, large trees growing in Brazil, is a yellowish liquid, 
of varying viscidity according to age, having a strong, terebinthinate, 
peculiar odor, and a bitter, burning, disagreeable taste. It mixes 
uniformly with absolute alcohol and volatile and fatty oils, and is 
readily dissolved by ether. It contains a volatile oil, a small quantity 
of soft, viscid resin, about fifty per cent, of a hard, acid resin, and a 
peculiar crystallizable acid, copaivic acid, which, according to Ber- 
natzik, is unimportant, the activity of the drug depending upon 
the oleoresin. 

Oleum Copaibae 8 to 15 minims (0.5-1 C.c). 

Physiological Action. — The local action of copaiba is that of 
an active stimulant or a mild irritant. When taken internally, it 
yields its active principle to absorption and elimination through the 
kidneys. The elimination takes place slowly, as Bernatzik found 
the oil in the urine as much as four days after its ingestion. 

Upon the general system copaiba has little influence; eighteen 
grammes of its volatile oil, taken in three doses during twelve hours, 
caused only a slight elevation of the pulse-rate and of the tempera- 
ture, with later vomiting and purging, and still later burning in the 
urethra and strangury (Bernatzik). In susceptible persons the evi- 
dences of the local action of the drug are more marked, it causing 
decided symptoms of gastro-intestinal irritation, accompanied by 
marked fever and irritation of the urinary organs, such as strangury, 
and even almost complete suppression. In Bernatzik's trials fifteen 
grammes of the resin, taken within five hours, produced violent 
purging and vomiting, with much abdominal pain. 

The discovery in 1841 by G. 0. Rey, that the addition of nitric 
acid to the urine of persons taking copaiba will produce a precipitate 
resembling that of albumin, has led to much discussion. To obtain 
this precipitate the copaiba must be freely given. As shown by 
Bernatzik, the precipitate probably consists of the oxidized oil united 



DIURETICS 553 

to some urinary principles. The copaiba-red of Quincke is a substance 
found in the urine of persons taking the oil of copaiba; it is an acid, 
whoso salts have the property of reducing the oxide of copper and of 
polarizing to the left, and may be a source of error in the diagnosis 
of diabetes. When a pure copaiba resin is used, although the 
copaiba-red cannot be detected in the urine, the urine still responds 
to Trommer's test for sugar. 

As a stimulant to the genito-urinary mucous membrane, copaiba 
is distinctly more active than buchu, but less irritating than the oil 
of turpentine. It may be used in chronic pyelitis and cystitis, but is 
chiefly employed in advanced stages of gonorrhoea; if administered 
during the height of the inflammation in these diseases, it is liable to 
aggravate the symptoms. It is also capable of affecting other mucous 
membranes than that of the genito-urinary tract, so that it may some- 
times be given with advantage in old indolent ulcers of the stomach, 
in chronic diarrhoea and dysentery, in advanced bronchitis, and especially 
when in chronic bronchitis there is very free muco-purulent expec- 
toration. As a local application it is sometimes very advantageous 
in chronic chilblains and other diseases of the skin. 

The only preparation of copaiba fitted for internal use is the oil. 

CUBEB. 

The unripe, but fully grown fruit of Piper cubeba, a climbing- 
plant of Java and other portions of the East Indies. These berries 
are blackish-veined, about the size of a small pea, and have attached 
to them a short stalk three or four lines long. Their odor is aromatic 
and peculiar; their taste warm, camphoraceous, and peculiar. They 
contain cubebic acid, cubebin, volatile oil, and resin, and are fully rep- 
resented by the official oleoresin. Bernatzik has found that cubebin 
is inert, which is in accord with the statement of Heffter, that cubebin 
passes through the alimentary canal without absorption, so that it is 
possible to recover from the feces almost the whole amount ingested. 

Official Preparations : 

Oleum Cubebae 10 to 15 minims (0.6-1 Co.). 

Oleoresina Cubebae 10 to 15 grains (0.6-1 Gm.). 

Fluidextractum Cubebae 15 to 30 minims (1-2 C.c). 

Cubeb is a local stimulant which has very little effect upon the 
general system. In large doses it produces a gastric and genito- 
urinary irritation proportionate in severity to the amount taken. 
Like copaiba, it occasionally causes an urticaria, which is probably 
due to the gastric irritation. It yields to absorption and elimination 
its active principles, which can be detected in the urine by the addition 
of nitric acid, when a precipitate resembling that of albumin occurs. 

In Bernatzik's experiments ten grammes of magnesium cubebate caused slight 
acceleration of the pulse and gastric uneasiness, with increased elimination of uric 
acid. Half an ounce of the oil, taken in thirty-six hours, produced very decided 



554 LOCAL REMEDIES 

gastric irritation, with the appearance in the urine of the oxidized oil in the form ->f 
a resin, and a very great decrease in the elimination of uric acid. After fifty gramni-.s 
of the powdered cubeb the gastro-intestinal irritation was most pronounced a>-d 
the nitric acid precipitate in the urine very abundant. 

Therapeutics. — Cubeb is used to relieve precisely the same 
conditions as copaiba. In many cases the best results are to be 
obtained by the combined employment of the two remedies. It has 
received much praise as an internal remedy in chronic hemorrhoids. 
It is useful as a local stimulant in the relaxation of the larynx fre- 
quently seen in public speakers following slight colds and overuse of 
the voice, chewing the berries often bringing relief to the throat and 
tone to the voice. The powdered drug may be used as a snuff in 
coryza. In this disease, as in all others, cubeb should not be employed 
in the earlier stages before secretion has been established, but later 
in the affection when the discharge is profuse. 

The best preparation for internal use is the oleoresin, which may 
be given in capsules. 

Matico, the leaves of the Piper angustifolium of Peru, contains 
a volatile oil, resin, and, it is said, a bitter principle, maticin. It is 
a softish mass which is largely employed as a styptic, and probably 
acts chiefly mechanically, coagulating the blood in its interstices, 
adhering to the wound, and thus arresting the hemorrhage. It has 
also been employed in internal hemorrhages and in gonorrhoea. In 
these affections it probably acts similarly to oil of turpentine, although 
much less of a stimulant and much more feeble. 

Fluidextractum Matico 1 fluidrachm (4 C.c). 

Juniper is the fruit of the common juniper, Juniperus com- 
munis, of Europe and this country. These berries are round, bluish 
bodies, about the size of a large pea, of a sweetish, terebinthinate, 
aromatic taste. They owe their properties to a volatile oil. They 
yield to boiling water and to alcohol. 

Official Preparations : 

Oleum Juniperi 5 to 10 minims (0.3-0.6 C.c). 

Spiritus Juniperi (5 per cent.) i to 1 fluidrachm (2-4 C.c). 

Spiritus Juniperi Compositus (4 per cent.) . .2 to 4 fluidrachms (8-15 C.c). 

Juniper is gently stimulant and cordial to the stomach. Upon the 
kidneys the oil exerts a decided stimulant action, and when freely 
given is capable of irritating the renal organs above the secreting point, 
and of producing lessened secretion, strangury, and even suppression 
of urine. Juniper is largely used as an adjuvant to potassium bitar- 
trate or the alkaline diuretics. On account of its stimulant local 
influence upon the alimentary canal, it renders the cream of tartar 
far more acceptable to the stomach, and at the same time aids its 
diuretic action. Sometimes juniper is employed for its stimulant 
action on the mucous membrane of the genito-urinary organs in 



DIURETICS 555 

chronic pyelitis ami in chronic catarrh of the bladder. Iii the form of 
the compound spun or its equivalent, gin, juniper is often useful in 
the Bubacute congestion of the kidneys frequently seen in old persons, 

ami characterized by aching in the loins and lessened urinary 
secretion without more serious symptoms. 

On. of Erioeron. — Erigeron Canadensis, or Canada Fieabanc, 
contains a large proportion of a yellowish volatile oil {Oleum Erig- 
troniis) of a rather pleasant odor and taste, which has properties 
resembling those of turpentine, but much less stimulating. It may 
be employed in affections of the genito-urinary organs and in passive 
hemorrhages. It is ('specially valuable in Menorrhagia. According 
to Starke, it is very efficacious in gonorrhoea. The dose is five to 
twenty minims (0.3-1.2 C.c.) every two or three hours, and is best 
administered on sugar. 

Oil of Santal (Oleum Santali) is a pale yellowish, strongly 
aromatic volatile oil, of a pungent, spiey taste, from the distillation 
of the wood of Santalum album. It is insoluble in water, but readily 
soluble in alcohol. When pure, it is a local irritant and probably 
capable of affecting the general system, although its physiological 
action has not been properly investigated. S. Rosenberg has noticed 
after doses of sixty drops a day irritation of the alimentary canal, 
burning in the urethra during urination, and an eruption of small 
red prominences upon the entire surface of the body, involving even 
the conjunctiva. Oil of sandal-wood is efficient in chronic bronchitis 
and in the 1 advanced stages of acute bronchitis, but its most popular 
use is in gonorrhoea after the first period of acute inflammation. From 
ten to twenty minims (0.6-1.2 C.c.) of it may be given, in capsule or 
emulsion, three or four times a day. 

Kava. — The root of Piper methysticum is used in the Sandwich Islands as the 
basis of an intoxicating liquor known as kava-kava, kawa, or ava. It contains a 
crystalline principle analogous to piperin, which its discoverer, Gobley, called 
methysHcin, besides an acrid resin, kavin, and a volatile oil. 

L. Lewin finds that when the kava resin is injected into the frog it produces 
a very pronounced loss of sensation at the point of injection, due to a paralysis of 
the j>eripheral endings of the sensory nerves, and that after the absorption of the 
remedy there is loss of voluntary motion and reflex activity, which is chiefly of 
spinal origin In experiments made upon the warm-blooded animals he obtained 
similar phenomena, — namely, local anesthesia at the point of injection, followed, 
after absorption, by general paralysis, due to a direct depression of the motor side 
of the spinal cord, the motor nerves and the muscles remaining intact. According 
to Dario Baldi, the active principle of kava produces in the dog a very short period 
of excitement of the sensory nerves, followed by a complete paralysis, at a time 
when the whole motor system still responds to stimuli. 

In small doses kava is said to act as a stimulant tonic, but when taken in large 
amounts to produce an intoxication which differs from that caused by alcohol in 
being silent, drow r sy, and without emotional exaltation. The great loss of muscu- 
lar power which is said to follow kava debauch in those unaccustomed to the use 
of the drug shows that its influence upon the spinal centres in man is the same as 
in other mammals. According to Baldi, Randolph, and Lewin, the resin of kava 



556 LOCAL REMEDIES 

is a local anesthetic of extraordinary persistency of action, but it appears to be too 
irritant for practical use. A decoction of the root is used in Oceanica very largely 
in the treatment of gonorrhoea, and its value has been strongly affirmed by Sanne. 
The dose of the root itself, given in decoction, is half a drachm (2 Gm.) three or four 
times a day: of a fluulextract, half a fluidrachm (2 C.c). 

Yohimbine. — This alkaloid is obtained from the bark of Corynanthe yohimbi, 
a rubiaceous tree, growing in the southern Cameroons district in Africa. 

It was originally investigated by Oberwarth and Loewy, who found it was 
in animals and also in man a very active excitant to the sexual organs and func- 
tions. On the other hand, Kravkoff, as the result of experiments upon the lower 
animals and upon man, concluded that it has no aphrodisiac effect; and frequently 
produces nausea, salivation, irritability, and other disagreeable results. It has been 
used, however, by numerous clinicians in neurasthenic impotence, with reports 
which are generally favorable to its influence. (For literature see Merck's Report, 
1901, 1902.) It is said to be of no value when impotence depends upon organic- 
nerve trouble, and to be harmful when it is caused by chronic inflammatory disease 
of the sexual organs or of the prostate gland. Dose, one-twelfth grain (5 Milligm.) 
of the hydrochlorate, either in tablet or solution, three or four times a day, 
hypodermically. 

HEXAMETHYLENAMINE. 

Hexamethylene-tetramine, is a condensation product of ammonia 
and formaldehyde. It is largely employed in medicine under various 
trade names, as urotropin, formin, aminoform, cystogen, etc. It 
occurs as colorless, odorless crystals, with a bitterish sweet taste, 
freely soluble in water, moderately soluble in alcohol, and with alka- 
line reaction. When gently warmed with dilute acid it is decomposed 
into formaldehyde and ammonia. 

Physiological Action. —Local Action. — Absorption and Elimina- 
tion. — Hexamethylenamine is distinctly irritant. It is absorbed with 
great rapidity, having been detected in the urine ten minutes after 
its ingestion, and is eliminated from the kidneys in great part 
unchanged, although, as first stated by Loebisch, it is to some extent 
decomposed in the organism with the liberation of formaldehyde. 

Casper injected urotropin under the skin of a rabbit and found formaldehyde 
in the blood, and also was able in some cases to detect formaldehyde in the urine of 
persons taking urotropin, an observation which has been confirmed by Suter, and 
by Citron. In a number of cases, however, these chemists failed to detect any 
formaldehyde in the urine, and P. J. Cammidge could not get it at all; so that it is 
evident that elimination of formaldehyde after the ingestion of hexamethylenamine 
is an inconstant phenomenon. It has been suggested that hexamethylenamine is 
decomposed by the acid juices of the stomach, but Suter found that when he put 
formaldehyde into the stomach of the rabbit, or took formaldehyde himself in safe 
dose, it was impossible to detect it in the urine; so that any formaldehyde liberated 
by the hexamethylenamine in the stomach would in all probability either be 
distributed in the system or tin-own off in some other form than formaldehyde. 

It has been shown by Suter that when urotropin is mixed outside of the body 
with acid urine it undergoes decomposition, although this does not occur when 
the urine is alkaline. It is therefore probable that that portion of ingested hexa- 
methylenamine which is decomposed suffers change in the kidney and upper urinary 
passages; a conclusion which is confirmed by an observation of Casper, that when 
the mine of a person who has taken urotropin is allowed to stand a continuous 
formation of formaldehyde goes on in it for days. 



DIURETICS 



:,;,7 



The bactericidal influence of hezunethylenamine in the urine is not altogether 
dependent upon its conversion into formaldehyde, since Cammidge has shown thai 
it has itself very marked bactericidal powers. 

Gnu nil Effects. — The ordinary therapeutic dose of hexamethyl- 
enamine produces no general symptoms, and we know of no cases of 
poisoning by it. In the dog the daily dose of two hundred and eighty 
grains is said to cause no other disturbance than renal irritation 
Nicolaier). The ingestion of one hundred and twenty grains a day 
of it usually causes in man burning pain in the bladder and urethra, 
especially after urination, followed, if the dose be continued, by the 
appearance of albumin, red blood-corpuscles, and abundant renal 
epithelium in the urine. P. J. Cammidge has noted after the free 
exhibition of urotropin general formication, especially intense at 
night, ending in a few days in a diffuse rash, suggesting that of measles. 

Therapeutics. — Hexamethylenamine was especially brought for- 
ward by Bardel and Laquers as a solvent for uric acid, but, according 
to the experiments of Arthur Nicolaier, it is less active in this respect 
than is piperazine, and is of no practical value for the solution of renal 
calculi. On the other hand, it ranks with piperazine as an altera- 
tive diuretic in the treatment of pyelitis, cystitis, and ammoniacai 
phospfwluria. In gonorrhoea it has failed to be of service. 

Our present experimental knowledge so strongly confirms the 
clinical experience of Citron that in order to get the good effects of 
hexamethylenamine in genito-urinary inflammations it is essential to 
maintain the acidity of the urine, that in most cases benzoic or boric 
acid should be exhibited at the same time as is hexamethylenamine.* 
Hexamethylenamine has been used as a prophylactic against nephritis 
in scarlet fever. Preisisch found 9 per cent, of kidney lesions with 
urotropin as against 13 per cent, without. Dose, fifteen to twenty 
grains (1-1.3 Gm.) three or four times a day, well diluted. 



REFERENCES. 



DIURETICS. 



Bocker Brit. For. Med. Chir. Rev., 

1854, xiv. 

Delbert C. R. S. B., 1896, iii. 

i Contrib. from Pepper Clin. 

Lab., 1900, 368. 

Meyer H. S. Jb., 1881, 345. 

Landauer Ungar. Arch. d. Med., 1894, 

iii. 136. 
Pobak and Bernheim. .Nouv. Arch. d'Obst. 

et Gvn., 1893, viii. 
Roix V. cle P., 1874, 578. 

STIMULATING DIURETICS. 

Bondztnski and Gottlieb.. A. E. P. P., 

xxxvi. 
Bbasse and Wirth. .C. R. S. B., 1887. 



cohnstein. . . . 
cohnstein. . . . 

Guam 

husemann . . . 
Jendrassik . . . 
kouindig-pom 
Lente. . . 



LuPINSKI 

Pawinski. . . . 

Sahashnikoi r 

ScHROFF 

SlEYA 



A. E. P. P., 1892, xxx. 

In. Dis. Berlin, 1892. 

Th. M., 1890, IV. 

Toxicologic, i. 413. 

D. A. K. M., 1886, xxxviii. 
l.KANTZ. .B. G. T., 1890. 
..Psychol, and Med. Leg. 

Journ., 1875. 
..H. S. Jb., 1883, 123. 
. .Vrach, 1893. 

. . In. Dis. St. Petersburg, 1892. 
. .Wb. G. A. W., 1864, 424. 
. .C. K. M., 1888, ix. 



SALINE DIURETICS. 

Albanese A. E. P. P., xxxv. 

Astalfoni A. I. P., 1903, xi. 



* The clinical experiments of Suter seem worthy of note. He found after fifteen grains of 
phenyl salicylate, boric acid, or benzoic acid were exhibited to a healthy subject at bedtime, the 
early morning urine made as good a medium for the growth of bacteria as ordinary urine; but if 
forty-five grains of hexamethylenamine or of phenyl salicylate were given the urine passed w;i- 
very inert towards bacteria; one to two days being required for the growth of bacteria in the salol 
urine, four days in the urotropin urine provided the urine was acid. Salol acted as well in the 
alkaline urine. 



558 



LOCAL REMEDIES 



REFERENCES {Continued). 



AuBEBTand Dehn. . A. G. P., 1874. 122. 

Bardet I.es Nouv. Rem., 1894. 

Bash am 1'ract. 1870, v. 

Binet K. M. S. R., 1892, viii. 

Bird On Urinary Deposits, 1859, 

3.56. 

Boi.tazi A. I. B., xxvi. 

Cahn A. E. P. P.. 1887, xxiv. 

Dehn A. G. P., xiii. 308. 

Doering M. M. W., 1903. 

Dogiel C. M. W., 1892. 

Duchi: Bull. d. 1. Soc. M<5d. de 

L'Yonne, 1884-80, 25-27. 

Falck A. G. P., 1889. 

Flint Amer. Med. Monthly, Oct. 

1800. 

Goon C. M. K. V., 1903. 

Gottlieb and Magnus . .A. E. P. P. 1900-01, 

xlv. 223. 
Hammer Prag. Med. Wochensch., 

1888, xiii. 
Htjsemann lourn. f. Pharmacodynani., 

1859, ii. 178. 

Kramer M. M. W., 1903. 

Kruger and Schmidt. .A. E. P. P. xlv. 
Laborde C. R. S. B., 1890, ii.; 1891, 

iii. 
Lenhartz Beitr. Path. Anat., etc., 

Festschrift, 1887. 
Marchand V. A. P. A., 1879, lxxvii.; 

A. E. P. P., xxiii. 
Meltzer International Contributions 

Festschrift, A. Jacobi 

New York. 
Mendel and Thachkr. .A. J. P., 1904, xl. 

Minkowski T. G., 1902. 

Mosaueb W. M. W. 1903. 

Munch Arch. d. Vereins. f. gemein. 

Arbeiten, 1803, 370. 

Nicholaier Z. K. M., 1899, xxxviii. 

Nicholaier and Hagenberg. .M. R., 1900. 
Parkes Brit. For. Med. Chir. Rev., 

1853, xi. 258, 1854, xiv. 

Pergami K. I. B., xxxiv. 

Podocaepow Y. A. P. A., xxiii. 1800, 

xxv. 400. 

Rabuteau 1. 'Union M<kl., 1871, 380. 

Riess B. K. W., 1882. 

Ringer and Morshead. .J. A. P., xii. 82. 
Ringer ami Mtirrell. ..J. P., i. 88. 
Sutkr 0. B S. A., 1901, xxxi. 



Tuloii Guy H. R., 1863, 177. 

Tmiengek M. M. W., 1903. 

Traube Gesammelte Beitrage, i. 386. 

Voit Handb. d. Allg. Stoffwech- 

sels, Leipzig, 1881. 
Von Mehing, (J) . Chlorsaures Kali, Berlin, 

1885. 

Wood, Jr A. J. P., 1898, i. 83. 

Wood and Arnold. .Phila. Monthly Med. 

Journ., April, 1899. 
Ulrici A. E. P. P., 1901, xlvi. 



ALTERATIVE DIURETICS. 



Baldi 

Bernatzik. 

Casper. . . . 
Cammidge. . 
Citron 



Cbdcib 

FLEIS< HMANN 

FORSTER 

Hari; 

Heffter 



Holmfeld. 
Hoppe 



.Iablonowski. 

ROBERT 

Laurentz. . . . 

Lewin 

Lewin 



LOEBISCH 

Maun i) 

MlALL 

Oberwarth and I 



Omelchenko. 
Preisisch 

Rosenberg. . . 
S A MX E 



hTARKK. 

Steppen 



Vi:iu\- - rvi{c)i)E an 
Von Mering 



S. Jb., ccxxxix. 

Prager, Vierteljahrs, 1804, 

lxxxi. 9; 1808, c. 239. 
1). M. W., 1897. 
L. L., Jan. 1901. 
Monats. d. Harn. u. Sex. 

Appar., 1898. 
Thesis, Paris, 1874. 
S. Jb., clxxx. 125. 
Aerztl. Intelligenzbl., 1881. 
M. News, Nov. 19, 1887. 
Atti dell. xi. Cong. Med. 

Internazionale, 1894, iii. 
Fort. M., Oct. 1, 1887. 
Journ. f. Pharmacodynam. 

105. 
In. Dis., Dorpat, 1858. 
C. M. W„ 1877, 129. 
In. Dis. Dorpat, 1886. 
V. A. P. A., 1883, xcii. 
Piper Methvsticum, Berlin, 

1880. 
W. K. W.. 1897. 
Annuaire de Therap., 1840. 
L. L., March, 1869. 
,oewy. .V. A. P. A., cliii.; 

B. K. W., 1900, No. 42. 
B. G. T., 1891. 
Ther. Geg., 1905. xlvi. 211. 
Th. M., 1887. 219. 
J. de Th. 1886. 
L. M. R., 1870 207. 
Untersuchungen, Wurzburg, 

1883. 
1 Nelson. ..I. M. R„ 1903, x. 
A. G. P., 1877, xiv. 270. 



FAMILY V.— DIAPHORETICS. 



Diaphoretics are those medicines which are employed to increase 
t be action of the skin. It is scarcely in place here to discuss the results 
of suppression of the functional activity of the skin or the importance 
of the surface-elimination to the system. It does seem well, however, 
to call attention to the fact that the perspiratory glands have a double 
function to perform, — that of elimination, already alluded to, and 
that of keeping down the temperature of the body during exposure 
to heat. When a man enters a Turkish bath the temperature of which 
is perhaps 160° F., or when he works in the sun on a very hot day, 
there is, if he be used to such exposure, little or no rise in the tem- 
perature of the body, because the surface-glands secrete sweat so 
actively as to expose a great amount for evaporation, and by the 
conversion of so much water into vapor such an amount of heat is 
absorbed — i.e., converted from heat into repulsive force — that the body 
is cooled. The reason that even a moderate degree of heat in a moist 
atmosphere is intolerable is because evaporation cannot take place. 

From what has already been stated, it is obvious that the use of 
dry external heat, or rather exposure to a hot atmosphere, is a power- 
ful means of producing perspiration. It may be applied either in the 
form of the Turkish bath, in which the air of the hot chamber is very 
dry, or in the Russian or vapor-bath* in which the atmosphere is 
surcharged with hot vapor. Neither of these baths has any other 
physiological property than that of a sweat-producer. 

Hot-water baths offer another very successful method of inducing 
profuse perspiration. The patient should be placed in a bath of 
about 100° F., and remain there from fifteen to twenty minutes, 
during which time, by the repeated addition of very hot water, the 
temperature should be raised to 110° F., or to such point as the patient 
can endure. Warmed blankets having been plentifully provided, the 
sick man should be lifted from the bath into them, be closely wrapped 
up, and so left for three or four hours before being transferred to the 
usual bed. According to A. Steffen, after this use of the bath the 
body has been proved to undergo loss of weight continuously for one 
or two days. 

The popular belief that after a sweat there is a greater liability 
than usual to take cold appears to us to be well founded: care must, 



* For home use there are in the market various "Cabinet Baths, " so called, which afford a 
cheap and efficient means of giving vapor-baths. The term Turkish bath is here applied to the 
bath used in this country under that name. This bath appears not to be a copy of the Oriental 
bath, but merely a derivative from it. Writers affirm that in the East the sudarium, or sweating- 
chamber, rarelv has a temperature of more than 98° F\: in London we have been in a Turkish 
bath at 200° I'.; from 140° to 160° 1". is a common temperature in American baths. 



559 



560 LOCAL REMEDIES 

therefore, be exercised to avoid exposure after the hot bath of any 
kind. The liability to take cold may, however, be overcome by the 
use of the cold douche or plunge-bath. 

The possibilities of the hot-water bath as a therapeutic measure are 
probably much greater than is ordinarily recognized. In severe burns, 
in nervous shock, and in various skin diseases continuous immersion 
would probably often be found of the greatest service. According 
to Baelz, the baths which are habitually taken by the entire 
native population of Japan are at a very high temperature (109° to 
114° F.), and the immersion continuous during the whole evening. 
The mouth temperature rises to 104° or 105° F., while the pulse 
becomes very full and increased in frequency, with marked evidences 
of relaxation of the arteries. When there is a high grade of atheroma, 
the softening of the arteries after an hour's bath is very pronounced. 
Baelz believes that there is no increase in the elimination of nitrog- 
enous matter, and that the Japanese custom is extremely useful, 
because, the winter being cold and the houses not heated, the people 
lose bodily heat during the day, and for two pennies in the evening 
acquire a supply of heat which lasts through the night. 

Profuse sweating is always more or less exhausting, but is not 
nearly so much so as purging, and therefore may be practised in 
dropsical patients too feeble to allow of the use of purgatives. The 
hot baths are not, however, altogether free from danger or objection. 
Sometimes in the Turkish and Russian baths the patient fails to sweat 
freely, and a feeling of distress, a bounding, rapid pulse, and perhaps 
severe headache develop themselves: under these circumstances the 
bodily temperature rises, and a fever develops, which may go on to 
the production of a true "thermic fever," and perhaps terminate in 
sudden death. This is an exceedingly rare result, and one that can 
never occur if the patient is removed from the hot chamber so soon 
as any unpleasant symptoms are manifested. Sudden death has 
been recorded once from "sunstroke" in a patient while taking the 
"Turkish bath," also once from "congestion of the lungs."* 

According to Steffen, the hot-water baths are contraindicated by 
the existence of congestion or cedema of the lungs, or of a tendency 
towards these disorders, since under such circumstances the bath 
greatly increases the disease, or precipitates a perhaps fatal attack. 
Our own experience corroborates these statements. We have seen, 
under the conditions mentioned, the most frightful dyspnoea result 
from the use of the hot-water bath. If disturbance of the respi- 
ration comes on during the bath, the patient should immediately 
be taken out, and, if the symptoms be urgent, cold water should be 
freely dashed over the head, neck, and chest. Severe cardiac disease is 
also a contraindication both to the Turkish and Russian or vapor-bath. 

Precisely as water may act as a diuretic by increasing the fluidity 
and amount of blood, so may it also act as a diaphoretic, provided 

* B. M. J., Oct. 1878. 



DIAPHORETICS . r »(il 

thai u is directed to the skin by being itself given warm and aided 
by the use of external heat; hence the importance of hot drinks 
when it is desired to produce free sweating. The colliquative "night- 
sweats" of phthisis are undoubtedly largely due to a paralytic weak- 
ening of the blood-vessels of the skin. In a similar manner aconite, 
veratrum, tartar emetic, and other substances which profoundly 
affect the circulation produce a free sweating which resembles that 
often seen in collapse from other than drug causes. 

Diaphoretics are employed in the practice of medicine to fulfil 
the following indications: 

hirst. — To arrest forming diseases of not very severe type, prob- 
ably by causing a flow of blood to the surface, and thereby relieving 
slight internal congestions, and possibly by eliminating principles 
which have been retained in the blood instead of being excreted as 
they ought to have been. In general cold, in muscular rheumatism, 
in suppressed menstruation, and other results of exposure to cold 
and of checked perspiration, the diaphoretics afford the most efficient 
means at our command for restoring the normal functions. 

Second. — To favor absorption. In dropsy the diaphoretics are of 
very great value, often aiding diuretics and purgatives in effecting 
a cure, and sometimes, when these fail, or when circumstances forbid 
their use, rescuing the patient from impending death. None of the 
medicinal diaphoretics except pilocarpine is of sufficient power to 
be relied upon in dropsy. The Turkish, the Russian, and the hot- 
water bath are capable of producing sufficient sweating to cause 
absorption of dropsical fluid, but must be vigorously employed. 

Third. — To aid in the subsidence of diseases which naturally pass 
off with a sweat. The chief use of diaphoretics for this purpose is in 
malarial fevers, especially in the remittent form of the affection, when 
t he sweating stage fails to develop itself thoroughly and the paroxysms 
run into one another. Even in the single paroxysm of intermittent 
fever, by hastening the closing stage, they often shorten the paroxysm. 

Fourth. — To eliminate noxious materials from the blood. The old 
humoral idea that the groundwork of such diseases as fevers is a 
distinct matcries morbi which can be eliminated from the blood has 
no sufficient demonstration to be accepted, and, although diaphoretics 
do good in fevers, yet it cannot be granted that it is in this manner. 
The very great power of increased diaphoresis in cooling the body 
through surface-evaporation has already been dwelt upon, and much 
of the good effected by diaphoretics in diseases of high temperature 
probably has its origin in this power. 

Modern science seems clearly to point out that diaphoretics may 
aid in separating from the blood retained secretions, and may to 
some extent replace the action of the kidneys when these organs are 
disabled by disease. 

In 1851 Schottin discovered urea in the sweat of patients suffering from the 
collate of cholera. Not only has the discovery of Schottin been confirmed by Iho 
36 



562 LOCAL REMEDIES 

researches of G. O. Rees, of Fiedler, of Hirschsprung, of Kaup and Jiirgensen, of 
Leube, and of G. Deininger, but it has also been abundantly proved that the skin 
excretes urea freely during the advanced stages of Bright 's disease, and also during 
the partial urinary suppression of scarlatinal desquamative nephritis. The urea 
in renal disease may even form a distinct crystalline powder on the skin, but it is 
most abundant about the mouths of the sweat-glands. We believe Landerer was 
the first to announce that urea is present in the sweat of healthy persons; and, 
although excellent chemists have been unable to detect it, its presence at times 
can no longer be denied, since it has been found not only by Landerer, but also by 
Funke in 1858, by Meissner, and by Leube; Fourcroy (quoted by Rees) has also 
found it in the sweat of horses. By a series of elaborate experiments, Leube has 
rendered it probable, if he has not actually proved, that in health there is such a 
relation between the skin and the kidneys that when the former is very active the 
latter excrete less than the normal amount of urea. 

When to the facts already cited are added the observation of 
Griesinger, that in diabetes the perspiration contains sugar, and the 
well-known circumstances that in rheumatism the sweat contains 
lactic acid, and in jaundice biliary products, the value of diaphoretics 
as a means of getting rid of retained excretions becomes manifest. 
For this reason, in Bright's disease, especially of the acute form, they 
are of the greatest value, acting beneficially in three different ways, — 
by drawing the blood to the surface, and thereby relieving any inter- 
nal congestions of the kidneys or other organs that may exist; by 
promoting the absorption of dropsical effusions; and by eliminating 
retained secretions. 

The drugs which are used clinically for the purpose of increasing 
the sweating are spirit of nitrous ether, tincture of aconite, powder 
of ipecac and opium, and pilocarpine. The spirit of nitrous ether 
acts by dilating the vessels thus inducing, so to speak, an artificial 
congestion of the sweat glands. Although for this purpose ethyl 
nitrite is used almost exclusively, it is evident that any of the nitrites 
is capable of fulfilling the same indication. 

It is probable that opium exercises a slight direct stimulant 
influence upon the sweat glands. Probably through the relaxing 
effects of nausea this action is greatly enhanced by ipecac so that the 
combination introduced by the famous pirate, Dr. Dover, has main- 
tained its place as a practical diaphoretic for two centuries and still 
remains one of the most valuable combinations for the purpose of 
producing sweating. 

PILOCARPUS. 

This drug, which has long been employed by the natives of South 
America,* received its first notice, under the various names oiJabo- 
randi, Jaguarandy, and Jamguarandi, from T. J. H. Langgaard in his 
Diccionario de Medecina domestica, Rio Janeiro, 1865. It attracted 
no attention, however, until 1874, when it was brought to Paris by 
Coutinho. The U. S. Pharmacopceia recognizes only the leaflets of 

* Under the name of Jaborandi various drugs other than the products of Pilocarpus are sold 
in Brazil. As the Pilocarpus pinnatus has been found to be active when grown in France, it is 
probable that the Jaborandi plant might be successfully cultivated in our Southern States, 
Frerichs (Berlin. Klin. Wochenschrif), 1875) found the wood inert, 



PI.UMIOHKTICS 



563 



two species, Pilocarpus Jaborandi and Pilocarpus microphyllus. 
These two shrubs are much alike, the leaflets of the compound leaves 
of t lie first variety are much larger than the second, being two to four 
inches long, while those of P. microphyllus are from one-half to one 
inch in length. Their activity is due to the alkaloid pilocarpine, 
discovered by Byarson.* They should contain not less than 0.5 per 
cent, ol total alkaloids. 

Official Preparations : 

Fluidextractum Pilocarpi J to 1 fluidrachm (2-4 Co.). 

Pilocarpine Hydrochloridntn i 1 : to J , grain (0.005-0.015 Gin.). 

Pilocarpine Nitras ^ to \ grain (0.005-0.015 Gm.). 

Physiological Action. — Local Action. — Absorption and Elimi- 
nation. Jaborandi is practically free from irritant properties, and 
yields its active principle rapidly in the alimentary canal. After 
hypodermic injection of pilocarpine the symptoms may set in in five 
minutes. It is probable that the alkaloid escapes from both the skin 
and kidneys. 

Qeneral Effects. — When an infusion of from sixty to ninety grains 
of jaborandi is given to an adult, in about ten minutes the face and 
neck become deeply flushed, and free perspiration and salivation 
commence. The sweating begins on the face; both it and the saliva- 
tion are excessively profuse, and last from three to five hours. There 
is not rarely nausea, and sometimes vomiting. The pulse is usually 
more or less quickened, as is also frequently the respiration. After 
the sweating has ceased, the patient is left more or less exhausted. 
The nasal ami lachrymal secretions are also very generally increased 
under the action of the drug, and Gubler has noted diarrhcea, which 
in the experiments of Ringer and others has not been present. There 
is sometimes contraction of the pupils, and even disturbance of vision. 
These effects of the drug are in the adult fairly constant; but sub- 
jects have been occasionally found who were not susceptible to the 
action of the remedy, and, very curiously, in Ringer's experiments 
children were found to be very insusceptible, although doses of sixty 
grains were employed. Schwann, Morat, and other observers have 
noticed in the lower animals that very violent gastric and intestinal 
movements are produced by the drug. 

Secretion. — The dominant action of pilocarpine is to increase the 
secretory activity of all the glands of the body, especially those of 
the skin. The action is either on the secreting cells themselves or, as 
appears at present probable, on the peripheral nerve terminals within 



♦Concerning llie alkaloids of jaborandi and their derivatives there is much confusion and 
imperfection in our knowledge. Three alkaloids have been thought to exist in jaborandi leaves, 
namely, pilocarpine and its derivatives, jaborine and pilocarpidine. According to its discoverers, 
Harnack and Meyer (.4. E. P. P., x\\.), jaborine acts upon the heart, pupil, intestines, and salivary 
glands in a manner almost identical with that of atropine, so that its occasional presence in com- 
mercial pilocarpine gives rise to vagaries of physiological and therapeutic action. Jowett, however, 
has been unable to isolate jaborine, and there is much doubt as to its being a constant constituent 
of jaborandi. (See Marshall. B. M.. 1900 ii.). Further, according to Marshall, jaborine sold by 
M -rck is a mixture of pilocarpine and a fourth alkaloid, isopilocarpine. Pilocarpidine, according 
to Harnack (.4. E.P.P., xx.i, causes in excessive dose violent sweating, salivation, also vomiting 
an I purging, with great disturbances of circulation. 



564 LOCAL REMEDIES 

the glands. On account of the antagonism between the skin and the 
kidneys the diaphoretic dose of pilocarpine may cause a decrease 
in the urinary flow, but the assertion of Gubler that the alkaloid 
administered in very small repeated doses has a marked diuretic 
influence has received clinical confirmation.* 

The sweat produced by pilocarpine is often enormous in quantity (nine to fifteen 
ounces by estimation). Vulpian has shown that the sweat is, as normally, alkaline. 
In the analyses of Robin the chlorides were found in excess, the carbonates and 
phosphates in very minute amount, and the urea in more than five times its normal 
proportion, the amount eliminated in the sweating being estimated at from ten to 
fifteen grains. Hardy and Ball believed that in their experiments the average 
amount of urea eliminated by the skin was seventeen grains. 

Jaborandi appears to have a stimulant influence upon secreting glands through- 
out the whole body. The nasal mucus is often greatly increased. The assertion of 
Pilicier, that in a dog with a gastric fistula the gastric juices were greatly increased 
by the drug, is in conformity with the free vomiting of large quantities of glairy 
secretion which it causes in man. Morat has noted a temporary increase of the 
sugar in the blood, an evidence that the glycogenic function of the liver is stimulated. 
The suprarenal capsules appear to share the action of the drug, since Auguste 
Pettit has noticed that in animals poisoned by jaborandi there is marked congestion 
and swelling of these bodies. According to Gottlieb, pilocarpine causes an increase 
of both the watery and solid constituents of the pancreatic secretion. 

There appears to be some relation between the flow of saliva and that of per- 
spiration produced by jaborandi: if the one is very profuse the other is often, but 
not always, correspondingly scanty. Sometimes the salivation almost replaces the 
sweating (Fereol); very frequently it commences before the sweating, and often it 
is more persistent. During it the mouth is warm, and there is often a feeling of 
tenseness about the maxillary glands. The saliva contains an abundance of salts 
and of ptyalin, as well as a small excess of urea. According to J. N. Langley, in the 
frog the mouth and skin, after the exhibition of jaborandi, become covered with a 
viscid secretion; in the dog, the rabbit, and the cat there is profuse salivation. 

That the action of pilocarpine in increasing secretion is direct and upon the 
glands themselves is shown by the fact, that the salivary glands are affected equally 
before and after section of all of the salivary nerves (Langley and Carville, confirmed 
by Schwann); also when the drug is injected directly into the gland and prevented 
from entering the general circulation (Langley). According to the elaborate experi- 
ments of Langley upon cats poisoned with pilocarpine, stimulation of the chorda 
tympani or of the sympathetic nerve causes respectively some increase or lessening 
of the secretion, but this increase or lessening is not nearly equal to that which 
occurs in the normal animal, and is due to the action of the nerves upon the circu- 
lation, and not to any influence on their secretory fibres. Very large doses of the 
drug injected into the gland immediately arrest the secretion, and doses of less 
size given in the same way, while increasing secretion, paralyze both chorda tympani 
and sympathetic nerve, so that stimulation of them has no effect. It is probable 
from the last fact that jaborandi has an action upon the secretory gland-cells. 

There is evidence that the action of pilocarpine is on the intrinsic nerves rather 
than the glandular structures. Atropine will check the salivation produced by 
pilocarpine and it is probable that atropine acts on the nerve endings. Moreover 

* Much interest attaches to the effect of jaborandi upon urea-elimination, but it cannot be 
considered as determined, except that in various diseases the combined renal and dermal elimi- 
nation is greatly increased by the drug. Hardy and Ball state that in health urea-elimination 
from the kidneys is diminished by the drug, while Tyson and Bruen have found it increased both 
in health and in disease. The experiments have, however, been too few, and especially the con- 
ditions of their performance too lax, for much importance to be attached to them. As the result 
of experiments upon the lower animals, J. Horbaczewski (Therap. Gaz., 1893) believes that there 
is a distinct relation between the elimination of uric acid and the number of leucocytes in the blood, 
and that pilocarpine in proper dose increases the size of the spleen and increases also the number 
of leucocytes in the blood and the quantity of uric acid eliminated. 



DIAPHORETICS 



565 



Fuchsinger (confirmed by NawrockH has found tliai seel ion of the nerves of the 
cat's leg did not prevent the paws from sweating when jaborandi was exhibited. 
But five or six days after the section, when the peripheral nerve-endings had under- 
gone degeneration, Fuchsinger found that jaborandi was unable to excite sweating. 

Jaborandi appears to stimulate the nutrition of the hair, and 
Prentiss, of Washington, has reported several cases in which the 
continued internal use of pilocarpine caused the hair to become 
exceedingly coarse ami to change its color from light to dark. H. 
Etasori has noticed a tuberculated eruption apparently produced by 
jaborandi. M. Grocco has found that pilocarpine hypodermicallv 
injected or locally applied sensibly affects hysterical anesthesia. 

Circulation. — Although very small doses of pilocarpine may 
produce an increase in the pulse rate, what is generally regarded as 
the characteristic effect in animals is a slowing of the pulse * with 
a rise of the blood-pressure. According to Harnack and Meyer the 
rise of pressure is an indirect action of the drug; the slowing of the 
pulse is brought about by a stimulation of the peripheral endings 
of the pneumogastric nerve. After toxic doses the blood-pressure 
falls, due to vaso-motor paresis. 

Although Harnack failed to obtain any evidence of primary increase in the pulse 
rate, the experiments of Kahler and Sayka, of Leyden, and of Reichert, demonstrate 
that if the dose is sufficiently small it does occur. The slowing of the pulse which 
occurs later is not prevented by previous section of the pneumogastric nerve but is 
at once set aside by an injection of atropine (Langley, Leyden, Harnack and Meyer) , 
as is also the diastolic arrest of the heart which pilocarpine produces in the frog. 
Since Ringer has shown that this antagonism between pilocarpine and atropine 
holds true for the ventricular portion of the heart, and since the cardiac muscle 
retains its normal irritabality it follows that the action of the drug must be upon 
the nerve terminals within the heart muscle. 

The rise of the arterial pressure is stated by Harnack and Meyer to be pre- 
vented by the use of curare and artificial respiration, and to be, therefore, a second- 
ary, not a direct, result of the drug's action: it is probably due to the convulsive 
muscular contractions produced by the drug. In the latter stage of the poisoning 
the arterial pressure falls. As in the experiments of Harnack and Meyer asphyxia 
in this stage did not cause rise of pressure, although the heart appeared still to 
retain its force, the vaso-motor system is probably paralyzed, a conclusion con- 
firmed by the later experiments of Reichert. The pulse still continues slow, 
although, according to Harnack, the vagi are completely paralyzed. 

Respiration. — According to the experiments of Morat and Doyon, 
pilocarpine produces a distinct slowness of the respiration, and as a 
respiratory poison is the antagonist to atropine, f 

Sexual Organs. — Jaborandi does not appear to have any power 
over the sexual organs, except the pregnant womb. Cases of abortion 
during its use have been reported by Masmann (quoted by Larvand) 
and by Schanta, but in the hands of other observers the drug has 
appeared to have little, if any, abortifacient influence, and Hyernaux 



♦The therapeutic dose generally produces in the human being quickening rather than 
retardation of the pulse. 

t H. Dreser (Arch. f. Exper. Path. u. Pharm., 1892, xxx.) has experimentally found that 
pilocarpine markedly increases the oxygen in the air of the swimming bladder of the carp. 



566 LOCAL REMEDIES 

and Chanteril have found it powerless in the lower animals (quoted 
by Larvand). When, however, the pregnant female is at her full 
term, the drug may affect the uterine contractions, as Larvand and 
others have noted an increase of the pains, or even a precipitation 
of labor, both in women and in the lower animals. Nevertheless, 
the oxytocic powers of jaborandi are very feeble.* 

Motor System. — In man, muscular tremblings have been observed 
during the action of jaborandi, but it is doubtful whether they are 
due to a direct action of the remedy. In the frog, as first noticed 
by Murrell, small doses (three milligrammes of pilocarpine) produce 
violent convulsions with heightened reflex activity, while larger 
amounts cause complete palsy. According to Harnack and Meyer, 
the convulsions are due to spinal stimulation, and the paralysis partly 
to overwhelming of the spinal centres and partly to paralysis of the 
muscles, the motor nerves themselves not being affected. The action 
of the drug upon the musculo-nervous system is entirely subservient 
to its other effects. 

Eye. — When applied to the eye, pilocarpine produces contraction 
of the pupil, tension of the accommodative apparatus, and an approx- 
imation of the near and far points of distinct vision. f Tweedy also 
states that there is impairment of vision, due to benumbing of the 
retina. According to P. Albertoni, the myosis is followed by a mod- 
erate but persistent mydriasis, and is not prevented by previous 
section of the oculo-motor nerve or of the upper cervical sympathetic 
ganglion. It is certainly the result of a peripheral influence. Gale- 
zowski, who uses a solution of one part of a pilocarpine salt in fifty of 
water, affirms that it answers as well as a solution of eserine in diseases 
of the eye, and has the great advantage of not producing irritation. 

Temperature. — Robin affirms that before and during the early 
stages of the sweating from jaborandi the temperature rises 1° to 2° 
F., but afterwards falls as much below the normal point and re- 
mains depressed for one or two days. This primary rise of temper- 
ature has been noted by other observers, J but is frequently absent 
altogether or very trifling. § The subsequent fall of temperature, 
which is a constant phenomenon, probably depends in great part, 
or altogether, upon the loss of heat during the sweating. 

Nutrition. — The interesting question whether the excessive secre- 
tion of solids from the skin and urine produced by pilocarpine 
is accompanied by any increase of waste products in the body, or 
is only due to an increased activity of the glands in clearing out 
waste products already produced, cannot at this time be answered. 
According to Otto Frank and Fritz Voit, the first dose of the alkaloid 

* See British Medical Journal. 1879, ii. 509; also Wien. Med. Blatt., 1879, ii. 1178, 1207. 

tSee John Tweedy (Lancet, 1875, i. 159), C. Scotti (Bed. Klin. Wochens., 1877, 143), and 
Galezowski (Med. Times and Gaz., 1877, ii. 358). 

1 See Ringer (Lancet, 1873, i. 157), Greene (Phila. Med. Times, vi. 56\ Scotti (Berlin. Klin. 
Wochens, 1877, 141), Pilicier (Med. Centralbl., 1876, 429), and Weber (Ibid.,770). PUicier noted 
that the rise occurred in the axilla, but not in the rectum: this would indicate that it is a local 
phenomenon, the result of a heating of the surface, not of the interior, of the body. 

I Consult Riegel (Berlin. Klin. Wochens., 1875, 86), Bardenhewer (Ibid., 1877, 8), and 
luschmann (Ibid., 353). 



DIAPHORETICS 567 

causes in the curarized dog increased elimination of carbonic acid, 
but a second dose, given when the carbonic acid elimination has 
returned to the normal, has no such effect; it is therefore probable 
that the drug has no direct influence upon nutrition. 

Therapeutics. — Jaborandi is by far the most reliable and 
powerful remedy of its class, and is always selected when it is desired 
to produce a very active sweating, as in uremia or in dropsy. Both 
in acute and chronic Bright' s disease it is of very great value, either 
as an aid to or as a succedaneum for the vapor-baths. The sweating 
should be repeated at regular intervals, varying from one a day to 
one a week, according to the nature of the case. 

Not only is jaborandi valuable for the removal of distinctly 
excrementitious material from the blood, but it is often of the greatest 
service in arresting the development of a forming disease, probably 
by eliminating peccant matters. Thus, in the onset of an attack of 
influenza, in the beginning of a bilious fever, and in subacute and 
muscular rheumatism it may often be used with great advantage. 
On the other hand, when in a fever it is desired not to produce a 
single excessive sweating, but simply to maintain moisture of the 
skin, jaborandi will hardly serve the purpose of the practitioner, 
and in typhoid or other asthenic fevers more or less danger of 
exhaustion attends its use. 

In doses of from one-twelfth to one-fifteenth of a grain (0.005- 
0.004 Gm.), given every two to four hours, pilocarpine usually causes 
a decided increase in the secretion of urine, and is a valuable remedy 
in the treatment of cardiac and of renal dropsies. In rare cases albu- 
minuria and even strangury * have followed this use of the drug, 
so that some caution would seem to be necessary in its employment 
in the early stages of acute nephritis. Nevertheless, we have seen it 
apparently successful in acute suppression of urine. 

In the treatment of pseudo-membranous laryngitis and in diph- 
theria pilocarpine was at one time extensively used, under the belief 
that by increasing the secretion beneath the membranes it would 
loosen them; it has, however, failed to establish its value for this 
purpose. Ringer has reported several cases of unilateral sweating 
cured by the use of full doses' of pilocarpine given hypodermically. 
It has been used with asserted success in alopecia. Cheron affirms 
that, when given in doses of one-twelfth of a grain hypodermically, 
pilocarpine is very effective as a galactagogue, but Cornevin found 
that in cows, at least, pilocarpine has no influence upon the quantity 
of milk secreted, though it increases the production of lactose. 

Locally applied (half-ounce of the leaves) in the form of a poultice, 
jaborandi may sometimes produce local sweating only, but we have 
seen marked and extraordinarily prolonged general sweating so caused. 

Ophthalmic Uses.f — The instillation of a one-per-cent. solution 
of pilocarpine hydrochloride into the eye is followed by exactly the 

* See Purjesz (Deutsch. Arch. f. Klin. Med., xvii. 533); also Stumpf (Deutsch. Arch., xvi.). 
t This section was written by Professor George E. de Schweinitz. 






568 LOCAL REMEDIES 

same results as those which have been described in connection with 
eserine. Pilocarpine fulfils all the therapeutic indications of eserine. 
It is not, however, as active, and therefore the strength of the 
solution used must be greater. It has the advantage of being less 
irritating and less liable to cause iritis. 

Administration. — Pilocarpine frequently causes much nausea 
and even vomiting, and we have found that when it is desirable to 
produce an excessive sweating for the purpose of breaking up a form- 
ing disease, much better results may be obtained by conforming to 
the following procedure than by giving pilocarpine unaided: let the 
patient, prepared for bed, take one dessertspoonful of a mixture 
containing, to the dessertspoonful, one-twelfth of a grain (0.005 Gm.) 
of pilocarpine hydrochloride, five grains (0.3 Gm.) of antipyrine, and 
three to ten minims (0.06-0.2 C.c.) of tincture of aconite-root; soak 
the feet fifteen minutes in a hot mustard bath; on getting into bed 
take a teaspoonful of the pilocarpine mixture, with a tumbler of 
very hot lemonade or whisky punch; repeating every twenty minutes 
the pilocarpine mixture until free perspiration sets in. 

Antagonism with Atropine. — In 1875 Langley called attention to 
the antagonism existing between jaborandi and belladonna. When 
the heart has been slowed or arrested by jaborandi, atropine will 
bring the rate of pulsation almost to normal; the reverse of this 
also occurs, provided the amount of atropine previously applied has 
not been too great (Langley). Upon the sweat-glands the two drugs 
have also antagonistic powers, one being able to annul the action of 
the other (Fuchsinger). The same is true in regard to the salivary 
secretion (Langley). This antagonism between atropine and jabo- 
randi is affirmed by H. Larvand to extend to the intestines and pupil. 
In belladonna-poisoning the alkaloid has been used with no advan- 
tage in very small dose, but in a case in which nine-tenths of a grain 
of atropine had been taken, nine grains of pilocarpine are said to have 
been injected hypodermically in between one and two hours with 
success (Purjesz). L. Juhasz reports a case in which it was estimated 
that about one and a half grains of atropine were taken, followed 
in half an hour by vomiting; four and a half grains of pilocarpine 
were injected in about seven hours, with a favorable result. Hofferts 
reports a case in which seven and a half grains of extract of bella- 
donna were ingested, and nearly two grains of pilocarpine given, 
with recovery.* 

REFERENCES. 

DIAPHORETICS. Fiedler In. Dis., Leipsic, 1854. 

_ ,. , „ , _ , . Fuchsinger A. G. P., xv. 482. 

Baelz Verhandl. d. Congress f. in- Funke U N M T vi 

r, n r er Sv. Me ^- ^ 9 ?o,- GoTTLiEB.'.'.";.'.';.'A.'E.'p.P.,'l894.xxxiii.261. 

Brown P. .1. Tr., March, 1857. Grocco L. M. R., 1882, 137. 

Carvh-le J. deTh., 1875. Hardy and Ball. .J. de Th., 1874. 

Cornevin C. R. S. B., 1891, in. Harnack and Meyer. .A. E. P. P., xii. 

Deininger D. A. K. M., 1869, vii. 587. Harnack A. E. P. P., xx. 

Fereol J. de Th., Jan. 1875. Hirschsprung . . .Gaz. des Hop., 1865. 

* For other cases of like import, see Lancet, 1890, ii. ; also Therap. Gaz., 1887. 



DIAPHORETICS 



56'J 



REFERENCES (Continued). 



HOFFERTS. 

J i u Lbs. . . . 



Kami. mi ani 
K in- and 



1 1 v \ . ; i n 



I Bai 
JURG 



Larvahd. 

Lei be. . . . 

I.I 1 DEN. . . . 
MsiBSNER. 

Mob it. . . . 
Mob \ i' ami 
Mcrri i 
Pettit 

I'll ICIER. 

Prentiss. . . 



Dot 



. Wien. Med. Press.-, lSS;t, 
rsiv. 1412. 
Klin. Monatsbl. f. Augen- 
heilk., w. 86. 
kv .Med. Centralb., 1876, 541. 
I nnsen. .1). A. K. M.. I860 
vi. 54. 
J. 1'., 1878, 339. 
J. A. P.. x. 1S8. 
H. M. J. Feb. 1875. 
La Pilocarpine, 1883. 
1). A. K. M . 1869, vii. :i. 

B. K. \\ .. IS77, 4()(i. 
. .In. Dis., Leipsio, 1859. 

Lyon M.. July, 1882. 
..n I'. K. S. 15., 1892, iv. 

P. .1. ami Tr., vi. L'L'S. 

('. K. S. B„ 1896, iii. 

Med. Centralb., 187ii. 130. 

P. M. T., xi. Oil). 



PCRJESZ, . 
K ISOR] . 

Rees 



Reichert. 
Ringer. . . 
Sch lnta. . 
schottin 



.Pest. Med. Cliir. Presse, 

1880. 
.Trans. Internat. Med. Cong, 

L881, iii. 146. 
. Enoyolopffldia of Anat., iv, 

841. 
U. M. M., 1893. 
. Pract. xvii., 401.; xxvi, 12. 
.W. M. W., 1878, No. 18. 
.Arch. f. Physiol, f It-ilk.. 

1851, xi. 



Schwann 
Steffen 

Vdlpian 


....Med. Oentrall)., 1875, 440. 
fahrb. f. Kinderheilk., 1871, 

iii. 
.... Lecons sur Subst. Toxiques, 

Paris, 1881. 87. 
'/.. B. 1902-03 \liv 




B. M. J., Oct. 1878. 
L. L„ 1876, i. 340. 



FAMILY VI.— EXPECTORANTS. 



Under the present heading we propose to discuss not only true 
expectorants, — that is, those medicines which have the power of 
influencing diseased conditions of the respiratory mucous membranes, 
— but also various substances and even various procedures which 
are employed for the relief of pulmonic conditions. 

Cough. — When from disease or from other causes obnoxious 
materials, be they secretions or foreign matters, accumulate in the 
bronchial tubes, cough is necessary for their expulsion, so that in a 
large proportion of cases no treatment of cough is desirable. On the 
other hand, there are cases in which, owing to excessive irritability 
of the pulmonic mucous membrane, the amount of cough is out of 
all proportion to the amount of material to be expelled. Under these 
circumstances the symptom is not only annoying, but also, by 
irritating the mucous membrane of the lungs and by exhausting the 
patient, directly harmful. In another set of cases, owing to muscular 
weakness and to lack of irritability of the mucous membrane, the 
cough is not sufficient for the expelling of the secretions, which gradu- 
ally accumulate in the lungs, fill up the bronchial tubes, and finally, 
it may be, cause death by a process comparable to that of drowning. 

It is plain that the medical practitioner must study in each 
individual case the relations between the cough and the amount of 
work required; so that if the cough be excessive it may be allayed, 
if it be insufficient it may be stimulated. For the purpose of allay- 
Mng cough, soothing vapors or liquids may be applied to the respira- 
tory mucous membrane by inhalations, but in the majority of cases 
^internal anodynes are necessary. 

In some instances the cough is maintained by an excessive irrita- 
bility in the upper throat and air-passages, so that demulcents such 
as liquorice are very useful, or relief may be obtained by sipping a 
mixture composed of glycerin and whisky, each one part, with two 
to four parts of water. 

The anodyne substances which are employed for the relief of 
cough are hydrocyanic acid, belladonna, hyoscyamus, chloroform, the 
bromides, morphine, codeine, and heroine. The action of hydrocyanic 
acid is too brief for the remedy to be of practical value. Belladonna, 
unless locally applied by means of atomization, is very uncertain 
in its action and of entirely secondary importance; superior to it 
is hyoscyamus, although even full doses of this remedy often 
are ineffective. Chloroform, in doses of ten to fifteen minims (0.6- 
0.9 C.c), sometimes acts mpst happily, but must be given at very 
570 



EXPECTORANTS 571 

short intervals on account of the fugaciousnesa of its influence, and 

is more useful in combination than alone. The bromides in full doses 
are often effective, and may well be combined with chloroform; in 
some cases they are too depressant. Much more certain in its influ- 
ence than any remedy yet mentioned is opium; its tendency to 
check secretion forbids its use, however, in a very large proportion 
of cases, notably in those in which there is persistent dryness of the 
bronchial mucous membrane, whether this dryness represents the 
first stage of an acute bronchitis or whether the case be one of a con- 
tinuing subacute bronchial irritation so frequent in neurotic indi- 
viduals. Moreover, the usefulness of opiates is further limited 
by their tendency to derange digestion, and in chronic cases by the 
danger of forming the opium habit. Under these circumstances the 
diacetiyl ester of morphine (heroine) is very valuable. 

We know of no method of increasing the irritability of the pul- 
monic mucous membrane when impaired. In such cases, if the loss 
of irritability be, as it usually is, dependent on general atony, strych- 
nine and cocaine may be administered in full doses, and are sometimes 
very serviceable. In an acute case, with failure to expel the secre- 
tion, as in the suffocative catarrh of infants, life may sometimes be 
saved by mechanical treatment. Stimulating emetics are often of 
the greatest service in freeing the bronchial tubes of secretion. On 
various occasions we have resuscitated young children after they had 
become completely comatose and lost the ability of swallowing from 
asphyxia due to suffocative catarrh, by the following procedure, 
which was suggested to us by the well-known reflex spasmodic con- 
traction of the respiratory muscles produced by a clash of cold water 
on the chest: 

Provide three tubs, one empty, one containing ice-water, and one with water at 
about 115° F. Hold the naked body of the child over the empty tub, and dash 
over the upper thorax a ladleful of the hot water, followed immediately by one of 
the cold water. So soon as the color of the skin has begun to change under the 
respiratory gaspings, and some evidences of consciousness appear, dip the body of 
the child momentarily in the hot water, when the scream produced by the pain will 
usually fill the lungs with air. In this procedure the hot water is used alternately 
with the cold water to prevent chilling of the body as well as to increase the shock. 

To allay Spasm. — When a spasm affects the laryngeal muscles 
acutely it may often be put an end to by an emetic dose of ipecacu- 
anha or, in a very robust subject, of lobelia; but in some cases, 
especially in so-called laryngismus stridulus, the exhibition of an anes- 
thetic may be necessary for the saving of life. In such cases chloro- 
form should be selected on account of the locally irritating influence 
of ether. Amyl nitrite in alarming cases often acts most happily. 
For the prevention of the recurrence of these spasms the various 
anodynes mentioned above may be employed. The most generally 
successful is the bromide, which in spasmodic croup should be given 
repeatedly in full doses. Local applications of belladonna — the 
smoking of belladonna cigarettes — are often very useful. 



572 



LOCAL REMEDIES 



In extreme cases of asthmatic bronchial spasm relaxation may be 
obtained by the exhibition, in robust cases, of lobelia in full doses, 
by smoking belladonna or stramonium cigarettes or pipes,* by the 
inhalation of amyl nitrite or chloroform, or by hypodermic injections 
of morphine or of heroine hydrochlorate. 

Local applications may be made to the lungs in the form of vapor 
or of fine spray obtained by the so-called pulverization of water. 

Atomization consists in breaking up by a mechanical contrivance 
solutions of a medicinal substance into a fine spray. At one time 
it was believed that in this way the finest ramifications of the bron- 
chial tubes could be reached, but the method has gradually passed 
out of use except for cases in which the disease is in the fauces, larynx, 

or trachea. In using atomization it 
must be remembered that it is only a 
means of making a local application 
to a certain part, so that the rules 
governing the choice of drugs to be 
employed are precisely those affecting 
local applications to other than the 
respiratory mucous membrane. - 

By atomization warm water may 
be applied as a diluent and as a sooth- 
ing application, its soothing proper- 
ties being capable of increase by the 
addition of cocaine, opiates, or other 
narcotic remedies. By atomization 
stimulant substances, such as ammo- 
nium chloride, also benzoates, carbo- 
lates, or other antiseptics, may be 
brought in contact with a diseased 
mucous membrane. When there is 
excessive secretion, as in bronchorrhoea, or hemorrhage, as in hemoptysis, 
the practitioner may use in the atomizer such astringents and hemo- 
statics as — tannic acid, one to twenty grains to the fluidounce; alum, 
from five grains to the fluidounce to a saturated solution; iron, Monsel's 
solution, five to fifteen minims to the fluidounce. In all cases in which 
strong local applications are being made to the lungs the occurrence 
of severe cough is an indication that the application is causing much 
irritation. 

For purposes of study the expectorants may be divided into two 
groups; (1) those which tend towards relaxation in the bronchial 




STEAM ATOMIZER. 

Fig. 19. — When steam is generated in 
boiler B, passing out through tube D, it 
draws up any medicament which may be 
placed in cup C; the mingled warm aque- 
ous vapors and drug are inhaled by the 
patient through A. The mode of treat- 
ment is of especial value in acute 
laryngitis and bronchitis. 



* There are upon the markets numerous proprietary mixtures for the relief of asthma by 
smoking; most if not all of them consist of powdered belladonna or stramonium, mixed with potas- 
sium nitrate and sometimes other substances. Clinical experience has shown that the efficiency 
of these powders is increased by the presence of arsenic, which probably acts by stimulating the 
bronchial mucous membrane to secrete freely. The following formula, taken from an old Phar- 
macopoeia of the Philadelphia Hospital, we have found to yield a very efficacious paper. 

Charta Arsenicaxis Composita (Compound Arsenical Paper). ty — Belladonna; fol., gr. 
xcvi; Hyoscyami fol., Stramonii fol., aa gr. xlviii; Extr. opii, gr. iv; Tabaci, gr. lxxx; Aqute, Oj: 
M., ft. sol. et add. Potas. nit., gr. clx; Potas. arsenit., gr. cccxx. Saturate bibulous paper and 
dry for use. Roll the paper into cigarettes, one of which is to be smoked two to six times a day 
until relief is afforded or some giddiness is produced. 



:\r MOTOR ANTS 



573 



blood-vessels and Increase of secretion, the so-called sedative or 

nauseating expectorants; (2) those which tend to overcome vascular 
relaxation and to diminish bronchial secretion. The first group are to 
be chosen in the early stages of an acute bronchitis, before secretion is 
established, while the "cough is tight;" the second group are more 
useful in chronic bronchitis or in the advanced stages of an acute 
condition. 

Of course, it must be understood that the division which has been 
made is arbitrary, and that very frequently there are conditions in 
which expectorants of one group may well be combined in one pre- 
scription with those of another group. Thus, ipecacuanha and 
ammonium chloride are often very serviceable in union. 



NAUSEATING EXPECTORANTS. 

One of the effects of nausea is an increase in the bronchial secre- 
tions; consequently any nauseating emetic acts, when given in smaller 
dose, as an expectorant. Those which are used practically in the 
first stages of a bronchitis are lobelia, antimony and potassium 
tartrate, ipecacuanha, potassium citrate, and apomorphine. 

Of these substances Lobelia is to be employed only in asthmatic 
cases in which there is distinct tendency to spasm of the bronchial 
tubes. The tincture may be given in doses of fifteen to twenty minims 
(1-1.3 C.c.) every three hours, or when a spasm amounts to a violent 
asthma, one fluidrachm (4 C.c.) may be exhibited every two hours 
until vomiting is produced. When large doses of lobelia are given 
the patient must be closely watched, as sometimes an alarming 
depression is produced. 

Antimony and Potassium Tartrate is similar in its expectorant 
influence to ipecacuanha, but much more powerful and much less 
safe. It should never be used in adynamic cases or with young chil- 
dren. Dose, as an expectorant, one-twelfth to one-sixth of a grain 
(0.005-0.01 Gm.), repeated according to circumstances. 

Ipecacuanha is very largely used in the early stages of acute bron- 
chitis, and is the safest of the nauseating expectorants. The dose of 
the syrup is from one-half to one fluidrachm (2-4 C.c.) every two to 
four hours, according to the exigencies of the case. 

Apomorphine Hydrochloride is a valuable sedative exjjectorant, 
useful in exactly the class of cases in which ipecacuanha is commonly 
given. 

Potassium Citrate, when given in large doses, perhaps because of 
its alkalizing effects, has a very notable effect in diminishing the 
viscidity and tenacity of the bronchial secretion during the dry stage 
of a bronchitis, and especially lends itself under these circumstances 
to combination with ipecacuanha, or in very robust cases with 
tartar emetic; one ounce (30 Gm.) of it should be given in the 
twenty-four hours. For many patients its taste is well concealed by 
lemon-juice. 



574 LOCAL REMEDIES 

Saponin. — The saponins are a group of glucosides more or less 
closely related both chemically and physiologically. Their name 
originated from their property of emulsifying fats and hence acting 
as cleansing agents. Some of them are highly toxic (these are called 
sapotoxins) while others are only feebly so. 

These glucosides are very widely spread throughout the vege- 
table kingdom, Robert giving a list of one hundred and forty plants 
which contain principles of the saponin class. According to the same 
authority, chemically pure saponin is physiologically inert, but saponin 
of commerce is a very active poison, and all of the plants containing 
it in considerable amount are capable of producing symptoms similar 
to those caused by commercial saponin. The symptoms caused by 
poisoning with saponin plants are violent vomiting and purging, 
the result of an intense gastro-irritation; convulsions; renal irrita- 
tion; alterations in the blood itself, — these plants being, in fact, 
actively toxic to all forms of protoplasm. 

On account of the irritant action of saponin on the stomach 
plants containing it reflexly increase the bronchial secretion, acting 
therefore as nauseating expectorants. 

Two drugs containing saponin in considerable quantity are recog- 
nized by the U. S. Pharmacopoeia, and, to some extent, used in 
practical medicine, — senega and quillaja. 

Official Preparations : 

Fluidextractum Senegse 10 to 15 minims (0.6-1 C.c). 

Syrupus Senegse (20 per cent.) 1 fluidrachm (4 C.c). 

Fluidextractum Quillajae 3 to 5 minims (0.2-0.3 C.c). 

Tinctura Quillajae (20 per cent.) 15 minims (1 C.c). 

Senega is the root of the indigenous Polygala Senega. It is used 
to a considerable extent in the United States as a stimulating expec- 
torant in the very advanced stages of acute bronchitis with free 
expectoration. It is really of little value, and causes in full dose 
much gastro-intestinal irritation. 

Quillaja or Soap-bark, the inner bark of the Chilean tree, Quillaja 
Saponaria, is probably the most actively poisonous of all the saponin- 
containing drugs. On account of its detergent properties, it is very 
largely used in the arts for cleansing silk and other fabrics. It is 
also employed as an emulsifying agent by the apothecaries, but its 
active physiological properties forbid such use of it. Robert recom- 
mends it as a cheap substitute for senega, given to the adult as a 
stimulating expectorant, a tablespoonful of a two- and a half-pcr-cenl . 
decoction. 

STIMULATING EXPECTORANTS. 

The so-called stimulating expectorants are more or less volatile 
irritating substances, which are partially eliminated by the lung and 
exercise a stimulant action on the bronchial mucous membrane 
during their excretion. Creosote, oil of eucalyptus, oil of turpentine. 



EXPECTORANTS 575 

and oil of sandal wood, which are important members of the group, 

are considered elsewhere in this treatise. 

Tkkpin Hydrate. — (Tcrpini Hydras.) — This derivative of oil of 
turpentine results from the action of nitric acid and water upon the 
oil of turpentine; the presence of alcohol facilitates its formation. 
It occurs in colorless, nearly odorless prisms, of a slightly aromatic 
ami somewhat bitter taste, nearly insoluble in water, soluble in 
alcohol. Terpin Hydrate is used in practical medicine as a stim- 
ulant expectorant, resembling in its action other members of 
the turpentine group, and is especially useful in the advanced 
stages of acute bronchitis when the secretion is unusually free. In 
our experience it is better borne by the stomach than is terebene, 
and is. in its action upon the lungs, scarcely distinguishable from 
that agent. It has also been used in chronic cystitis, and in gonor- 
rhcea. It may be given in doses of from three to six grains (0.2-0.4 
Gm.) four to six times a day, in capsules. 

Tf.rebene (Terebenum) is a clear, colorless liquid, almost insoluble 
in water, isomeric with turpentine, and of a peculiar odor, some- 
what resembling that of freshly sawed pine wood. It is prepared 
by the action of sulphuric acid upon oil of turpentine. 

Terebene, one of the most effective of the stimulant expectorants, 
was first recommended by William Murrell. It is very useful not 
only in chronic bronchitis, but also in the acute disease after the earlier 
stages have passed by. As an expectorant it is nearly equivalent 
to the oil of eucalyptus, but is more stimulating. It has also been 
employed with asserted good results in dyspepsia, especially in the 
flatulent intestinal variety, and may be used in chronic or subacute 
inflammations of the genito-urinary tract. Its action upon the general 
system has not been investigated, but probably resembles that of 
oil of turpentine. From twenty to forty minims (1.3-2.5 C.c.) of it 
may be given to the adult in the course of twenty-four hours. It 
lends itself well to use by inhalations, either by atomization of water 
containing it or by vaporization from hot water. The vapor should 
be as concentrated as can be borne without exciting cough. 

Tar (Pix Liquida) is a black semi-liquid substance, of peculiar 
odor and taste, obtained by the destructive distillation of various 
species of pine. The tar used in this country is almost exclusively 
the product of the Pinus palustris of North Carolina and other of the 
Southern States. In composition it is very complex. When distilled, 
it yields an oily liquid, known as oil of tar, pyroligneous acid, and a 
solid, black residue, pitch. It is freely miscible with alcohol, ether, 
and the fixed and volatile oils, and also to a slight extent in water. 

The virtues of tar undoubtedly reside chiefly in the oil. This 
is a complex body containing creosote, phenol, and several allied 
compounds besides toluene, xylene and other bodies of minor impor- 



576 LOCAL REMEDIES 

tance. According to Taylor, the oil of tar has produced death in 
man. To cause death, tar itself would have to be ingested in enormous 
quantity, since a sailor (according to Stille) recovered after taking 
between a pint and a quart of it. 

Official Preparations : 

Oleum Picis Liquidae 3 to 5 minims (0.2-0.3 C.c.;. 

Syrupus Picis Liquidae (5 per cent.) 1 to 2 fluidrachms (4-8 C.c). 

Unguent um Picis Liquidae (50 per cent.) External use. 

Tar is used internally solely in the advanced stages of obstinate 
acute bronchitis, or in chronic bronchitis. Locally, it is much employed 
in chronic diseases of the skin, as a stimulant antiseptic application 
in the form of the official ointment. In many cases this is too severe, 
and the strength must be reduced. Hebra states that if it be applied 
too freely enough of the tar may be absorbed to darken the color of 
the feces and the urine, and even to cause gastric irritation and black 
vomit. For internal administration the most elegant preparation is 
the Syrup of Tar. 

Grindelia. — This is the leaves and flowering tops of Grindelia 
robusta and of Grindelia squarrosa, plants inhabiting the extreme 
western portions of North America. In commerce the whole herb, 
including the stems, roots, and floral heads, is sold. The taste is 
warmish, peculiar, and very persistent. The presence of a crystalline 
alkaloid in grindelia has been asserted by several investigators, but 
at present it seems probable that its activity depends upon a 
turpentine-like volatile oil. 

Fluidttxtractum Grindelia? 30 to 60 minims (2-4 C.c). 

Physiological Action. — The toxic powers of grindelia are said 
to be so feeble that three drachms of the nuidextract are required to 
kill a rabbit. According to Bufflngton, it produces narcosis with 
dilated pupils by a cerebral influence, but acts more powerfully in 
paralyzing the nerves of sensation and the sensory side of the cord, 
and finally attacks both the motor cord and nerves. Buffington also 
affirms that it causes in warm-blooded animals a slowing of the action 
of the heart by stimulating the inhibitory apparatus, and an eleva- 
tion of the blood-pressure by stimulating the vaso-motor centres. 
Dobroklowski states that the large but non-toxic doses increase the 
pulse-rate as well as the arterial tension by a direct influence upon 
the heart or the peripheral vessels; that in toxic dose the drug 
depresses the pulse-rate and the arterial tension, and finally arrests 
the heart in diastole. 

Therapeutics. — Grindelia has not been employed for its effect 
upon the circulation, and in the doses used in medicine it appears to 
exert no distinct influence upon the heart or arteries. It has been 
largely used, often with alleged excellent results, in asthma, and in 
bronchitis associated with a tendency to bronchial spasm. It is prob- 



EXPECTORANTS 577 

able that in tlu-so cases it not only has a relaxing influence, but also 
stimulates the mucous membrane, and even in chronic bronchitis, 
especially oi the aged, it is said to do good. It has been employed in 
whooping-cough. Its active principles are probably excreted by the 
kidneys; hence after large doses there are sometimes evidences of 
renal irritation, and in chronic catarrh of the bladder good has been 
effected by its stimulant influence upon the mucous membranes of 
the viscus. It has also been employed as a local application, with 
alleged good results, in vaginitis. The fumes of burning grindelia 
are sometimes inhaled with alleged relief in asthma. The plant should 
be steeped in a solution of nitre, dried, and burnt upon a plate, or 
may be smoked in cigarettes or in a pipe. 

Balsam ok Peru {Balsamum Peruvianum) is obtained from 
Toluifera Pereirae, a tree of Central America. This balsam is a viscid, 
honey-like, fragrant, brownish fluid, of a warm, bitterish taste, which 
has been shown by Brautigam and Nowack to be practically devoid 
of antiseptic properties. According to Fremy, it contains not benzoic, 
but cinnamic acid. It has been used in chronic catarrhs of the respira- 
tory and genito-urinary systems; dose, half a fluidrachm (2 C.c.). 

Balsam of Tolu (Balsamum Tolutanum) is obtained from Tolui- 
fera Balsa mum, a tree very closely allied to that which yields the 
balsam of Peru. Balsam of Tolu is at first a thick, plastic solid, but 
by time it is converted into a hard, translucent, resinous solid. Its 
odor is highly fragrant and its taste vanilla-like. It contains cinna- 
mic acid and a volatile oil, and its medical properties are the same as 
those of the balsam of Peru. On account, however, of its grateful 
taste, it is preferred to the latter, and is very much used to flavor 
medicines, especially cough-mixtures. In full dose, every three hours, 
it may be of some value in chronic bronchitis, but as generally used 
its preparations are simply agreeable vehicles. 

Official Preparations : 

Balsamum Tolutanum 15 to 30 grains (1-2 Gm.). 

Tinctura Tolutana (20 per cent.) \ to 1 fluidrachm (2-4 C.c). 

Syrupus Tolutanus (1 per cent.) i to 1 fluidounce (15-30 C.c). 

There are a number of expectorants of very small value, but requiring notice 
on account of their being in use. Ammoniac (Ammoniacum), an irritant gum- 
resin, was formerly used to a considerable extent in chronic bronchitis in doses of 
from twenty to thirty grains (1.3-2 Gm.); of the emulsion (Emulsum Ammoniaci 
— four per cent.), one to two tablespoonfuls may be given. Horehound (Marrx t bium, 
U. .S.) contains a volatile oil and a bitter principle, marrubiin; also tannin. It is 
u>ed domestically to a considerable extent in catarrhs of the upper respiratory tract. 
Dose of the powder, thirty grains to one drachm (2-4 Gm.). Bloodroot (Sangtjin- 
aria, U. S.) is in overdoses an emetocathartic and narcotic poison. It contains 
sanguinarine and other alkaloids, and has been used in chronic bronchitis, but has 
no practical value. Dose of the fluidextract (Fluidextractum Sanguinari.e, 
I . S.), two minims (0.1 C.c). Sanguinarine is a violent poison, causing in mammals 
vomiting, purging, collapse, convulsions, loss of reflex activity, cardiac depression, 
and finally death from asphyxia. (For details see eleventh edition of this treatise.) 
37 



578 



LOCAL REMEDIES 



Sulphuretted Hydrogen. — In 1886 Bergeon proposed a method of treating 
phthisis by filling the large intestine with sulphuretted hydrogen diluted with pure 
carbonic acid gas. After an extraordinary but very brief popularity the method has 
fallen into such complete desuetude that it is only necessary here to refer to the 
tenth edition of this treatise for details. 

Sulphuretted hydrogen is, however, a valuable remedy in the treatment of 
purulent pulmonic catarrhs, whether of tubercular or other origin. When, under 
any circumstances, a bronchial catarrh is accompanied by very free expectoration 
the remedy may be useful in relieving the mucous membrane. We have also found 
it of service in chronic gout, when administered persistently for months. The method 
of administration employed by Bergeon was barbarous and absurd. The sulphu- 
retted hydrogen may be given by the mouth in the form of a natural sulphur-water 
or, better, by means of water saturated with sulphuretted hydrogen and carbonic 
acid gas. The dose of the saturated solution is two to four ounces (60-120 C.c), 
three or four times a day. In some cases it produces digestive disturbance, and its 
use has to be abandoned. That the gas is absorbed and eliminated by the lungs is 
proved by the very perceptible odor upon the breath. Many of the sulphur springs 
of Europe have inhaling chambers, and experience has shown that the sulphurous 
vapors are of value. 



REFERENCES. 

EXPECTORANTS. Kobert Chem. Centralblatt. 1893, 

Bergeon C. R. A. S., July, 1885. ,. „ 1 - 32 i _, ,„„ 

Bocker Beitr. z. Heilk., ii. 170. AIuhrell B. M. J., Dec. 188o. 

Brautigam" and Nowack. .C. K. M., 1889, Rabuteau L'Union Mdd., 1871, xii. 

xxiv. 329. 

Buffington A. J. M. S.. Jan. 18, 1886. Stewart Chloride of Ammonium, 

Dobroklowski.. . C. M. W., 1885, xxiii. 321. Rangoon, 1870. 



FAMILY VII.— EMMENAGOGUES. 



Emmbnagogtjes are medicines which are employed to promote 
the menstrual flux. In the great majority of cases amenorrhcea is 
merely a symptom of some constitutional disorder, as chlorosis, or 
tuberculosis, and is to be regarded rather as a conservative symptom 
than one to be relieved, and, therefore, the emmenagogues have 
largely gone out of use. In some instances, however, it is possible 
that the molimen may be checked as a result of some nervous influ- 
ence and re-establishment be desirable. The drugs which are used 
for this purpose are mostly remedies which are local irritants and 
are supposed to act by stimulating the uterine mucous membranes. 
Cantharides and guaiac, which are sometimes used for this purpose, 
are considered in other portions of this book. 

Savin. — The dried tops of Juniperus Sabina, a juniper, native 
of the south of Europe and the Levant, contain a turpentine-like 
volatile oil. This oil is a powerful irritant. When taken in sufficient 
dose, it produces severe abdominal pain; incessant vomiting and 
bloody purging; diminution or even suppression of the urine, which 
is often albuminous and bloody; disordered respiration; symptoms 
of disturbed innervation, such as unconsciousness, stertorous breath- 
ing, and convulsions or convulsive tremblings; the scene closing by 
death in collapse. In pregnant females, abortion, accompanied by 
violent flooding, almost always occurs before the fatal issue. After 
death, signs of gastro-intestinal inflammation are generally present, 
but in some instances these are wanting, and in one case reported 
by Letheby pulmonary apoplexy and congestion of the brain were the 
chief lesions. 

Official Preparations : 

Oleum Sabinse 3 to 5 minims (0.2-0.3 C.c). 

Fluidextractum Sabinae 10 to 20 minims (0.6-1.2 C.c). 

Although in rare cases of menorrhagia dependent upon uterine 
relaxation, the oil of savin is useful, its importance is chiefly owing 
to the frequency of its domestic use as an abortifacient, — a use which 
is accompanied by the gravest danger to life and has often ended in 
death. 

Rue. — The leaves of Ruta graveolens, or common garden rue, contain a volatile 
oil whose properties are similar to those of oil of savin. It has been used in Europe 
for the production of criminal abortion, but seems to be less employed than is the 
oil of savin, and to be less dangerous, as we have met with no records of death from 
it except that of a man weakened by dysentery.* According to M. Helie, taken 

* Case of G. F. Cooper (Med. Eiaminer, N. S., ix. 720). 

579 



580 LOCAL REMEDIES 

internally, in large doses, it causes violent gastric pains, excessive and sometimes 
bloody vomiting, profuse salivation and swelling of the tongue, great prostration, 
confusion of mind, and convulsive twitchings, with, in pregnant women, abortion. 

Tanacettjm. — The common tansy of the gardens, Tanacetum vulgare, in the 
form of decoction, or of its volatile oil, is sometimes used as a stimulant emmen- 
agogue or for the purpose of producing abortion, but is a very unsafe remedy. When 
taken in sufficient amount it causes abdominal pain, vomiting, loss of consciousness, 
and violent epileptiform convulsions.* The minimum fatal dose of the oil of tansy 
is not known, but in two cases a teaspoonful of the oil produced violent epilepti- 
form convulsions, and the same amount is said to have caused death. Recovery is 
stated to have occurred after two teaspoonfuls (Whitehill); also after three flui- 
drachms. The action of the oil upon the lower animals has been studied by Guillery. 
In frogs the most important effects which it was found to produce were paralysis of 
the peripheral endings of the motor nerves, with early appearance of post-mortem 
rigidity; and paralysis of the vaso-motor centre of the medulla and of the inhibitory 
cardiac apparatus, with at last paralysis of the heart itself. In warm-blooded ani- 
mals the oil produced symptoms precisely similar to those which it causes in man. 
After section of the spinal cord the convulsions did not occur in the hind legs; they 
are therefore of cerebral origin. The arterial pressure was not affected until death 
was at hand: so that it is evident that the drug has little action upon the heart. 

Oil of Hedeoma. — Under the name of oil of pennyroyal, in the United States, 
the oil of the Hedeoma pulegioides (Oleum Hedeoma:, U. S.) is used as a stimulating 
emmenagogue in domestic practice, but has very little power. Two fluidrachms 
taken by a young woman produced vertigo, faintness, muscular weakness, frequent 
feeble pulse, cold skin, and cold extremities (C. A. Bryce). Dose, from two to ten 
minims (0.12-0.6 C.c). In Europe the oil of Mentha pulegium is known as oil of 
pennyroyal. 

Apiol. — Apiol is a peculiar non-nitrogenous, yellowish, oily liquid, 
which is obtained from the root of the Apium petroselinum, or com- 
mon parsley. According to its discovers, Joret and Homolle, one 
gramme of it will produce in man a cerebral excitation very similar 
to that induced by coffee, without other symptoms. In doses of 
from two to four grammes it causes a species of intoxication, with 
vertigo, ringing in the ears, and severe frontal headache, — a group 
of symptoms very similar to those seen in cinchonization. 

Apiol has been used to a considerable extent as an antiperiodic. 
but it is certainly of very inferior rank. It was originally recommended 
in amenorrhea by Joret and Homolle, who exhibited three or four 
grains twice a day for a week preceding the time in which the return 
of menstruation was due. Whenever any symptoms of the men- 
strual molimen appear, fifteen grains (1 Gm.) of it should be admin- 
istered in the course of three or four hours. It is always given in 
capsules, each of which, as imported from France, usually contains 
one-quarter of a gramme (3.9 grains). 

Potassium Permanganate, originally recommended by Sydney 
Ringer as an emmenagogue, has been very highly commended by 

* For references to cases see Guillery; also Cincinnati Lancet Clinic, 1881; A. J. M. S. xvi., 
xxiii., xxiv. ; Med. Bull., 1888, x. Guillery believes that the symptoms caused by the oil and by 
tansy tea are different. In a case of poisoning by the leaves, however, reported in the Nashville 
Med. a.nd Surg. Journ., 1879, xxiii., the symptoms were those alleged to be characteristic of 
oil-poisoning; and the oil probably is the only active principle of the drug. 



EMMENAGOGUES 



:,.s i 



Fordyce Barker and other physicians." Therapeutic doses of the 
permanganate musl be entirely decomposed in a very short time 
after they reach the stomach, so that any action which the drug 
exerts upon the general system is due to the manganese oxide; indeed, 
the ordinary black manganese oxide has been affirmed by various 
practitioners to be as active an emmcnagogue as is the permanga- 
nate. We have employed these agents to a limited extent in func- 
tional amenorrhoea, sometimes with, sometimes without, success. 
The only difference which we have been able to perceive in their 
action is that the permanganate is the more irritant to the stomach. 
The dose of either preparation may be set down as one to two 
grains (0.06-0.13 (!m.), — always administered after meals, in order to 
avoid, as far as possible, gastric irritation. Cases of severe gastritis 
produced by the permanganate have been reported. 

Viburnum Opulus. U. S. — Cramp-root. Viburnum Prunifo- 
LTOM. U. S. Black Haio. — These remedies are believed by various 
practitioners to be of value in the treatment of dysmenorrhea and 
menorrhagia, and ovarian irritation. 

Fluidextraetum Vibumi Opuli 1 to 4 fluidrachms (4-15 C.c). 

Fluidextraetum Vibumi Pnmifolii 1 to 4 fluidrachms (4-15 C.c). 

REFERENCES. 

EMMENAQOOUES. Joret and Homoli.e. .Joum. de Pharmacie, 

3 s., xxviii. 219. 

Brtce Southern Clinic, iv. 323. Letheby L. L., 1845. 

GuiLLBRY B. A. R. B., 1878, xii. Whitkhili J. A. M. A. xlvii. 509. 



* See Therap. Gaz., n. and iii. 



FAMILY VIII.— OXYTOCICS. 



Oxytocics are those remedies which are employed during or 
directly after parturition, to increase the uterine action. Of the 
few drugs which have claims for position in the present class, quinine 
has already been fully considered; it apparently differs entirely from 
the other known oxytocics in not producing continuous tetanic spasms 
of the uterus, and is therefore the safest stimulant to parturition at 
our command. The peculiar dangers which beset the use in labor of 
drugs which cause uterine tetanus will be fully discussed in the article 
upon ergot. 

ERGOT. 

Ergot is a blackish body, one to two inches in length, irregularly 
cylindrical, grooved along one side, and very generally curved; it is 
composed of very thick walled microscopic cells, containing oil-drops 
but no starch. As was first demonstrated by Tulasne, ergot is the 
sclerotium of the Claviceps (C. purpurea, Tulasne) which infests the 
grain of Secale cereale, or rye. 

Among the lowest of vegetable organisms, and distinguished from all other 
plants by the absence of chlorophyll, are the fungi. There are in most cases two 
distinct states or stages in the life of a fungus: in the first of these, the vegetating 
period, it exists as a mycelium, a usually filamentous mass or flocculus, whose sole 
function is to grow and increase; in the second stage the thallus, or ordinary fungus 
or mushroom, is formed, and to it is assigned the function of developing repro- 
ductive bodies, after whose maturation it perishes. Between these stages there is in 
some fungi an intermediate one, in which the plant exists as a sclerotium. The 
genus Claviceps comprises a number of parasitic fungi, which develop in the pistils 
of the various species of Gramineae. The first appearance of the ergot is in the 
flower of the rye, at the base of whose pistil there arises a minute flocculent mass 
of mycelial filaments. These filaments, continually growing and invading all parts 
of the tissue of the pistil, at last form of it an irregular whitish body, at the base of 
which after a time appears a dark-colored body, the sclerotium, which continues to 
grow, lifting up the diseased and withering mass formed out of the original pistil, 
and finally developing into a perfect ergot. If a fresh, living ergot be placed in a 
damp, warm place, after a time little cracks wiU appear in its surface, and tlirough 
these cracks little round bodies will project, and finally be raised up on stalks and 
constitute perfect thalli, — minute fungi, which finally produce spores. 

Ergot is an exceedingly complex substance, containing nearly 
thirty-five per cent, of an inert fixed oil. 

A large number of chemists have claimed to have isolated the active principle 
of ergot, only to have their claims denied and replaced by the discoveries of the next 
chemist who invades the field. Kobert isolated a tetanizing alkaloid to which he 
gives the name of cornutin, which he found also to be a powerful stimulant to the 
uterus. He also described an active acid body to which he gave the name spha- 
celenic acid. Jacobi found a resinous acid sphacelo-toxin which was apparently 
582 



OXYTOCICS 5S3 

identical with Robert's sphacelenio acid, which forms a number of combinations 
with other constituents of ergot. Vohlen describes :i crystalline body, clavin, which, 
he claims, stimulates the uterus but does not affect the blood-vessels. Barker and 
Pale have found a substance, ergot oxin, which they regard as a hydrate of the alka- 
[oid ergotinin discovered by Tanret, which they regard as the active principle. 
To which, if any of these substances, ergot owes its activity it is impossible to say. 
The term ergot in lias been applied to a variety of substance, but to-day is most 
commonly understood to refer to Bonjean's ergotin, which is practically a watery 
extract of the drug. 

Official Preparations : 

Fluidextractum Ergotse 1 to 4 fluidraehms (4-15 C.c.). 

Extractum Ergotse 5 to 8 grains (0.3-0.5 Gra.). 

Vinum Ergotse (20 per cent.) J to 2 fiuidounees (15-60 C.c). 

Physiological Action. — Local Action. — Absorption and Elimina- 
tion. — The preparations of ergot have a very feeble local action, but 
their irritant properties are sufficient to interfere with their hypo- 
dermic use. and sometimes to make them disturb the stomach. They 
yield their active principles readily to absorption, but concerning 
the fate of these bodies in the organism we have no knowledge. 

General Effects. — According to Diez (quoted by Stille), the prin- 
cipal effects of poisonous doses of ergot are in the lower animals 
profuse salivation, vomiting, dilatation of the pupils, hurried breath- 
ing, frequent pulse, cries, trembling, staggering, paraplegia, in some 
cases diarrhoea and urgent thirst, convulsions, and death.* 

Among the lower animals chickens are most susceptible to the action of ergot. 
In these it produces, besides ataxia and general weakness, a cyanosis of the comb 
and wattle which become, if the dose has been sufficient, finally gangrenous and 
fall off. So marked is this effect that it has been used as a method of determining 
the comparative activity of different specimens of the drug. It is asserted that in 
pigs the tips of the ears become gangrenous. The mortification is due to obstruc- 
tion of the arteries by a transparent hyaline mass following a local vascular spasm. 

The toxic effects of ergot on the lower animals are mainly paralytic, 
and the only ones which are in any sense characteristic are the anes- 
thesia and the coldness of the surface. As this coldness of the surface 
has been noted in various women in whom the drug has caused fatal 
abortion, it is probably characteristic of the poisoning. 

Nervous System. — The action of ergot upon the general nervous 
system is extremely feeble, but is not well understood; as both 
Wright and Kohler have found that the voluntary muscles are not 
affected by the drug, the motor symptoms of the poisoning would 
appear to be of nervous origin.* The statement of Eugene Haudelin, 
that the peripheral nerves are not affected, has been confirmed by 
the experiments of Kohler, so far as concerns the motor nerves and 
the watery extract of the drug. 

According to Kobert cornutine acts as a convulsant but sphacelotoxin is a 
motor depressant. A specimen containing excessive amounts of cornutine may 

* In 1884 T. Korkorin, in a St. Petersburg thesis, affirmed that pronounced and character- 
istic pathological alterations can be found in the spinal cord of animals slowly killed with ergot. 
The correctness of this, however, seems to be more than doubtful. See paper by A. Griinfeld 
(Archir f. Psych, u. Nerven., 1889-90, xxi). 



584 LOCAL REMEDIES 

therefore cause spasms but ordinarily from preparations of ergot itself, as shown 
by S. A. Wright the paralysis is much more marked than the spasms; in some 
cases the special senses seemed to be destroyed, and coldness of the surface was a 
very prominent symptom. He foimd that the intravenous injection of a strong 
infusion caused immediate dilatation of the pupils, great increase in the rate of the 
cardiac pulsations, paralysis, and convulsions and death in a few minutes: when the 
dose was not sufficient to kill at once, great anesthesia and coldness of the skin and 
also paralysis of the special senses were developed. In Kersch's experiments intrave- 
nous injections of the poison caused marked coldness of the surface and also great 
muscular rigidity. Upon rabbits, according to Wright, ergot acts very feebly. 
Enormous doses of ergot are required to produce toxic symptoms in animals, since 
in one of Wright's experiments an amount equivalent to two drachms for every 
pound weight of the dog failed to kill. 

Circulation. — The characteristic action of ergot upon the circu- 
lation is to cause a rise of blood-pressure by constriction of the blood- 
vessels probably through stimulation of the vaso-motor centres. 
After very large doses the blood-pressure is lowered probably chiefly 
by weakening of the heart muscle although there may be also a toxic 
widening of the vessels. 

In 1870 Charles L. Holmes found that ergot injected into the jugular vein of 
a dog caused a sudden immediate fall of the blood-pressure, followed in a short time 
by a marked rise above the normal. This fact has been confirmed by Kohler and 
Eberty, by H. C. Wood, by Kobert and by Jacobi. Plumier, however, asserts that 
the rise is insignificant, and in the experiments of Sollman and Brown it was either 
absent entirely or else very slight. The most probable explanation of the results 
obtained in the last two investigations is found in the ease with which ergot 
undergoes spontaneous decomposition. Houghton examined some two hundred 
specimens of ergot, many of which he found to be quite inert. 

The primary fall of pressure is probably due to the depressant action of an 
excessive amount of the drug, which reaches the heart in concentrated form when 
thrown into the vein, directly upon the cardiac muscle. 

The rise in pressure, which is to be regarded as the characteristic effect of ergot 
upon the circulation, is due to a constriction of the blood-vessels. Holmes, Wernich, 
Vogt, Kersch, Schuller and Boldt assert that they have seen invariably diminution 
in the caliber of the arteries under the influence of ergot.* According to Wood, 
Hemmeter and Kobert the rise in pressure does not occur after section of the spinal 
cord, and is therefore consequent upon a stimulation of the vaso-motor centre in 
the medulla. 

There is however some evidence that it also exerts some direct stimulant 
influence on the vessel-walls. The evidence which has been brought forward in favor 
of the direct stimulant action of ergot upon the blood-vessels fibres consists of the 
statements of Holmes, Wernich, and J. H. Peton, that after the nerves going to 
certain blood-vessels have been cut, these vessels can be seen to contract when 
ergot is injected into the animal. The observations of Holmes, Wernich, and Peton 
are, however, in distinct contradiction to the very elaborate experiments of Paul 
Vogt, in which the dilated vessels in the ear of the rabbit whose cervical ganglion 
had been extirpated could not be made to contract by ergot. Moreover, any obser- 
vations made with the eye as to the contractions or dilatations of the blood-vessels 
are of doubtful value. 

Greater importance should be attached to the experiments of Ringer and Sains- 
bury, made upon tortoises according to the method of Gaskell (see Digitalis, 
page 224). In these the addition of ergotin greatly slowed the rate of flow through 
the arterioles, but in these experiments it was found that the addition of ergotin to 

* Patrick Nicol and J. Mossop (Brit, and For. Medico-Chir. Rev., 1872, 1) have noted with 
the ophthalmoscope the contraction of the retinal vessels after the exhibition of ergot in man. 



OXYTOCICS 585 

tlif saline solution used had no distinct effect until there whs ten per cent, of the 
extracl in solution, enough to seriously influence the viscidity of the solution, and 
probably the effecl of the ergotin was the resull of altered physical conditions. 

They have, however, received some confirmation in the investigations of 
Plumier who found that perfusion through the pulmonary vessels separated from 

the central nervous system produced a slight constriction of these vessels, and of 
Jaoobi, who found that the rate of How through the vessels of the leg was 
diminished when perfused with ehrysotoxin. 

According to the observations of Parola, Gibbon, Beatty (quoted by Still6), 
and Bailly and See, very large doses of ergot reduce the pulse-rate in man, hut 
only under the rarest circumstances below sixty. Meltzer and Auer observed that 
under the influence of ergot the vagus is abnormally sensitive to electrical stimula- 
tion. Eberty found that in the frog the drug still lessened the rate of the cardiac 
beats after destruction of the medulla, but that in the atropinized mammal ergot 
was powerless to alter the cardiac rhythm. By toxic doses the rapidity of the heart's 
action is increased, and, according to Boreischa, galvanization of the par vagum 
lias at this time little or no effect upon the pulse. It may be that ergot first stimu- 
lates and then paralyzes the peripheral pneumogastric, but before any conclusion 
can be considered established further investigation is imperative. 

As has been shown by Haudelin, Boreischa, Brown-Sequard, and others, the 
toxic dose of ergot produces immediately or after a time a fall of the arterial pres- 
sure. The assertion of Brown-Sequard, that this fall of arterial pressure is due, at 
least in part, to a vaso-motor paralysis, is corroborated by the experiments of 
Boreischa, who found that when the vessels were paralyzed by section of the spinal 
cord high up. the fall of pressure produced by the toxic dose of ergot was proportion- 
ately not nearly so great as in a normal animal. The fall of pressure however is 
brought about also through cardiac failure for Hemmeter and Plumier demonstrated 
tliat the isolated heart is slowed and weakened by large doses of ergot and Eberty 
found that the heart is arrested in diastole and non-irritable. 

Bodily Temperature. — The coldness of the surface in ergotic 
poisoning seems to depend upon a general fall of temperature. Hem- 
meter has noticed that this fall of temperature commonly amounts to, 
and often exceeds, 5° C. in the lower animals and 2° F. in the human 
being. The cause of it has not been made out. Hemmeter states 
that in several experiments he has found pronounced reduction of 
urea elimination in dogs under the influence of ergot, and believes it 
possible, though not proved, that the fall of temperature is due to 
diminished general metabolism; it may, however, be only a secondary 
phenomenon -due to the action of the drug upon the circulation. 

Action on the Intestines. — The muscle-fibres in the coats of the 
blood-vessels are certainly not the only non-striated muscles influ- 
enced by ergot. According to Wertheimer and Magnin, ergot pro- 
duces active movements in the coats of the stomach, and Wright 
found very active intestinal peristalsis at the post-mortem examina- 
tions of poisoned animals; further, Wernich, Haudelin, and Meltzer 
and Auer bear witness to the violent intestinal peristalsis produced 
in the lower animals by toxic doses of ergot. 

Uterus. — Upon the uterus of parturient women or of the parturi- 
ent lower mammal ergot exerts a very pronounced and fixed influ- 
ence, increasing the length and force of the pains, and, if it be given 
in sufficient dose, causing after a time violent tetanic cramp of the 
whole organ. 



586 LOCAL REMEDIES 

The action of ergot in producing contraction in the impregnated 
but not parturient womb is by no means so constant. Clinical experi- 
ence shows that in pregnant women it often fails to originate uterine 
contractions. Upon animals Wright found it to fail in all of a number 
of trials, as did also Bonjean in a single experiment. On the other 
hand, Diez,* Oslere,* and Percy and Laurent * found it to cause 
abortion in guinea-pigs, sows, rabbits, cows, and cats; and Bodin 
has reported an epidemic of abortion occurring among cows near 
Trois Croix, which he attributed to feeding upon ergotized grasses. 

Our present knowledge indicates very strongly that the uterine 
contractions produced by ergot are of centric origin. It is true that 
some years ago Boreischa asserted that he had succeeded in producing 
violent uterine movements with ergot after division of the nerve 
connections of the organ, but the result reached by Wernich — namely, 
that no vermicular movements are produced in the unimpregnated 
womb after previous section of the spinal cord — has received con- 
firmation from John C. Hemmeter. In repeated experiments, having 
found that the injection of ergotin produced contractions in the 
exposed uterus of a narcotized rabbit, he destroyed the spinal cord 
with a hot wire, and determined that ergot was no longer able to 
cause uterine contractions: that the failure of the ergot in these 
cases was not due to paralysis of the uterus by shock was then demon- 
strated by injecting ammonia into the veins, when violent uterine 
contractions occurred. 

SUMMARY.— Therapeutic doses of ergot increase blood-pressure 
by stimulating- the vaso-motor centre in the medulla, but have no 
distinct influence upon the heart or the walls of the arterioles. 
Toxic doses depress the pressure by cardiac paralysis, and prob- 
ably also by paralysis of the blood-vessels. Ergot, in full thera- 
peutic doses, so acts upon the centres in the lower spinal cord 
which preside over the uterine muscles as to produce in the partu- 
rient womb violent uterine contractions, and finally uterine tetanus. 
It also increases the peristaltic movements of the stomach and 
intestines. 

Therapeutics. — Ergot has been used in medicine chiefly for 
three purposes: (1) to increase the uterine contractions, (2) to check 
hemorrhage, (3) to contract the blood-vessels in chronic congestions 
and over-secretions depending on vascular relaxations. 

1. — Owing to the power that ergot possesses of intensifying 
labor-pains, it has long been used in uterine inertia during parturition. 
Indeed, it was for this purpose that the drug was first employed 
in medicine, and thereby acquired the name of pulvis parturiens. 
The literature of the subject is immense, and all imaginable opinions 
as to the effects of the drug when given in labor, and as to the advis- 
ability of its employment, have been advanced; but, without dis- 
cussing these, we shall here simply point out the clearly established 

* Quoted by Stills (.Therapeutics, 2d ed., ii. 585,1. 



OXYTOCICS 



f)S7 



rules for its use and the clinically determined dangers and advan- 
tages of its employment. If ergot be given in very small doses during 
labor, the natural pains arc simply intensified; but if the dose be 
large enough to have a decided effect, their character is altered: 
they become not only more severe but much more prolonged than 
normal, and finally the intervals of relaxation appear to be completely 
abolished and the intermittent expulsive efforts are changed into 
one violent, continuous strain. It is evident that, if the resistance 
be sufficiently great, this may endanger the safety both of the mother 
and of the child. The dangers to the mother are twofold: there is a 
possibility of the uterus rupturing itself by its efforts; and, when the 
head comes down upon the perineum, if the soft parts be rigid there is 
a very strong probability that they will be lacerated. The danger of 
uterine rupture is, we think, a remote one; for although several 
alleged cases have been recorded, yet in very few is the accident 
clearly traceable to the asserted cause. The fatal character of the 
accident is such, however, that the possibility of its occurrence should 
always prevent the reckless use of the drug. 

The improper use of ergot is even more serious in its effects upon 
the child than upon the mother. During a violent uterine contrac- 
tion the passage of the blood from the placenta to the child must be 
interfered with, or, in other words, the respiration of the foetus is 
temporarily stopped, so that its life depends upon the aeration of 
the blood during the intervals. If the latter be very much shortened, 
the life of the child is greatly imperilled; and if they be abolished, 
it must be destroyed, unless delivery occurs in a very few moments. 
These considerations are, we think, sufficient, without further discus- 
sion, to show the imperativeness of the rule neve?' to give ergot in 
uterine inertia when there is much resistance, either in the bony or 
in the soft parts of the mother. In primiparse such resistance is 
always to be looked for, and its degree often difficult to judge of 
beforehand; and in such women ergot should not be used for the 
purposes of expulsion. Even under the most favorable circumstances 
— when the woman has previously borne children, when the bony 
pelvis is capacious, and the soft parts are relaxed and dilatable — 
its use should be entered upon with caution; and if the accoucheur 
be skilful in the application of instruments, cases must be rare in 
which the latter are not preferable to the ecbolic. 

In women of lax fibre, with roomy pelves, ergot may be cautiously 
used in uterine inertia if instruments are not at hand, or if they are 
objected to, or if the obstetrician is timid in their application. 

At the close of parturition, ergot is very commonly employed to 
prevent post-partian hemorrhage; and in this case there is no objection 
to its use, and the remedy is invaluable. But, as it requires from 
fifteen to twenty minutes for its action when given by the mouth, 
ergot exhibited in this way cannot be relied upon to arrest flooding 
when it has already set in. To prevent the occurrence of the latter, 
it is an excellent rule to give a full dose of the ecbolic when the child's 






588 LOCAL REMEDIES 

head is well down upon the perineum and beginning to emerge at the 
vulva. After labor, if a tendency to bleeding is manifested, ergot 
may be administered hypodermically. 

For the induction of premature labor, ergot has been and still is 
to some extent used; but it is uncertain in its action, and offers no 
advantages over instrumental methods. 

In 1872 Hildebrandt announced that in nine cases of fibroid tumors 
of the uterus he had used with the utmost advantage hypodermic 
injections of ergotin, and this practice has been followed very widely 
on this continent. It is scarcely to be doubted that cures are some- 
times effected; but probably in the majority of cases * the drug 
simply lessens the uterine congestion, and does good precisely as it 
does in chronic or subacute metritis and in subinvolution and hyper- 
trophy of the uterus (Meadows) ; it may be that sometimes it strangles 
the growth by causing uterine contractions. If the latter be the case, 
a cure, as is suggested by Goodell, is to be expected from the remedy 
only in mural and sub-mucoid tumors. 

2. — The success of ergot in arresting hemorrhage after labor soon 
led to its use in uterine hemorrhages in other than parturient or 
pregnant women; and the next step beyond this was its employment 
in other hemorrhages. In all forms of hemorrhage in which no direct 
local application can be made, ergot is to-day still largely used. 
The use of ergot as a styptic in an internal hemorrhage is based on 
its power of contracting blood-vessels. It must be remembered 
however that any substance which leads to a general vaso-constric- 
tion increases the force of the circulation. The increased pressure 
tends to dislodge any clot which may be formed at the bleeding 
point. Therefore those drugs which narrow the lumen of the vessels 
must incline to continue rather than check internal hemorrhages. In 
uterine hemorrhages it acts by causing contraction of the uterus 
itself, not of the blood-vessels. 

3. — Very many years ago F. E. Barlan-Fonta}'ral proposed the 
use of ergot in chronic dysentery and diarrhoea, on account of its power 
of causing contraction of the capillaries; and Massolaz, in an epi- 
demic of chronic diarrhoea among the French troops serving in the 
East, found that the suggestion was well timed. Although Barlan- 
Fontayral afterwards published a book upon the subject, it attracted 
little or no attention. In 1871 A. Luton, of Rheims, stated, as some- 
thing new, that he had used ergot with remarkable success in a violent 
and protracted epidemic of dysentery. Successful cases of chronic 
diarrhoea are also reported by other observers, so that trials of the 
remedy should be made in all obstinate cases. 

In colliquative night-sweats due to relaxation of the blood-vessels, 
ergot is a most efficient remedy. Another employment of ergot for 
the purpose of restraining excessive secretion is in galactorrhcea, in 

* See Amer. Journ. Med. Sci., July, 1873; Amer. Practitioner, May, 1873, May, 1874, August, 
1874; Clinic, April, 1873; Lancet, May, 1873; Chicago Med. Juurn., 1874; and especially Byford's 
Address (Trans. Amer. Med. Assoc, 1875). 



OXYTOCICS 589 

which affection it Ha* been used with success by Le Gendre, who was 
led to employ it by an observation of Poyet and Commarmond, that 
wet-nurses fed upon ergotized bread lost their milk. 

The action of ergol upon the blood-vessels suggests its employ- 
ment in those cases in which there is local or general dilatation of 
the vessels. We have used it in pulmonic congestion with apparent 
good results, and it has been highly lauded in the first stages of pneu- 
monia by X. S. Davis, by Sunol, and later by other clinicians. It has 
been especially noted by J. E. Kelly, as giving immediate relief when 
injected hypodermically in low forms of pulmonary hyperemia, such as 
occur in typhoid fevers. Ergot has also been recommended by 0. 
Rosenbach, as a means of raising blood-pressure in cases of cardiac 
disease where there is thought to be insufficient peripheral resistance; 
and Hemmeter believes that the dicrotic pulse is due to a very low 
degree of pressure in the arterial system, and is an indication, espe- 
cially in chronic cardiac disease, for the use of ergot. Rosenbach 
recommends the drug strongly in aortic insufficiency with cardiac 
dilatation. Ergot would seem to be indicated as a vaso-motor stimu- 
lant in surgical shock, but is much less prompt in its influence than 
atropine. 

As originally suggested by Brown-Sequard, it is still much used 
for the relief of chronic cerebral and spinal congestion. When there 
is a rupture of the vessels, as in apoplexy, by increasing the blood- 
pressure it tends to do harm rather than good. It is largely used for 
the relief of congestive headaches, and has been employed in epilepsy, 
in which disease, according to Hemmeter, it greatly increases the 
efficiency of the bromides. Dehenne states that he has obtained most 
remarkable effects in the relief of diabetes by subcutaneous injections 
of ergotin. The general clinical experience, however, seems to be 
that while occasionally ergot does great good in diabetes, it usually 
fails to accomplish anything. When successful, it rapidly diminishes 
the glycosuria, thirst, and polyuria. In diabetes insipidus, though it 
often fails, ergot is perhaps the most generally useful remedy that 
we have. 

Da Costa has used ergot with asserted good results in enlargement 
of the spleen from various causes and affirms that he has even cured 
leukemia with it. 

Toxicology. — Even the largest therapeutic doses (an ounce of 
the fiuidextract) produce in man no perceptible symptom save some 
nausea. In a number of cases death has resulted from abortion caused 
by large doses of ergot, but we know of but two instances of serious 
poisoning in a non-pregnant person.* 

In the first case gastric irritation, thirst, diarrhoea, burning pain 
in the feet, and convulsions are said to have preceded death. In the 
second case (G. S. Oldright), two hours after taking the drug (amount 
not stated) there were developed tingling in the fingers and feet, 



• Davidson reports u case with fluid blood, jaundice, and universal hemorrhages, attributed 
with doubtful correctness to poisoning by ergot (London Lancet, 1882, ii. 526). 



590 LOCAL REMEDIES 

cramps in the legs, arms, and chest, with dizziness and weakness; 
the pupils were dilated, the pulse was very small, and a feeling of 
coldness was complained of. These symptoms were relieved by the 
administration of stimulants and the use of external heat; after a 
time they recurred with greater violence; finally, under the reinstitu- 
tion of the measures previously employed, the face became intensely 
congested and purplish red, pain in the head was felt, the patient 
seemed much excited, and convulsions were feared, but did not occur; 
there was some diarrhoea, with dark gray stools. 

Chronic Poisoning. — Since the days of Galen there have swept 
over larger or smaller districts of Europe epidemics of diseases which 
have been attributed to ergot. In many parts of Europe rye bread 
forms the great staple article of food of the lower classes. It always 
contains a small quantity of ergot, but not enough to have any 
deleterious effect upon the health. When the summer is wet and cold, 
the rye becomes very extensively ergotized, so that the fungus con- 
stitutes a large proportion of the materials entering into the bread. 
It is under these circumstances that there occur epidemics of ergotism 
or chronic ergotic poisoning. It is not always the rye that causes 
these frightful losses of life, as Heusinger has traced one epidemic 
to diseased oats. Before going further, it seems proper to state that 
Trousseau and Pidoux assert that these epidemics are not dependent 
upon any specific action of ergot, but are either epidemics of blood 
diseases or simply the results of improper and insufficient food, — the 
outcomes of poverty, wretchedness, and famine. It seems to us 
indisputable that some of the various epidemics which have been 
recorded were of this character, but certainly it is no less indisputable 
that others were not. Moreover, numerous scattered cases are on 
record in which a few persons or a family have been affected with 
ergotism unmistakably traceable to the use of bread largely composed 
of the fungus.* 

The scope of the present treatise is such as to forbid our entering 
into an elaborate discussion of the epidemics of ergotism, especially 
as the subject has no practical bearing so far as the American pro- 
fession is concerned, since the absence of deep poverty is so complete 
in our country that no one would feed on largely ergotized bread; 
and, in fact, no case of ergotism has as yet been recorded as occurring 
in the United States. f 

There are two varieties of ergotism, — the gangrenous and the 
spasmodic. In some epidemics the cases have been of mixed type. 

Gangrenous ergotism has been especially observed in France, and is believed 
to be the same as the Ignis Sacer or the Ignis Sancti Antonii of the Middle Ages, 
— an affection which in 922 killed forty thousand persons in Southwestern France, 
and in 1128-29 fourteen thousand in Paris alone. It generally commences with 
itching and formications in the feet, severe pain in the back, contractions in the 

* For an account of a modern epidemic, see Deulsch. Arch. f. Klin. Med., xxxiii. 246. 

t Any one especially interested in the subject will find the literature very well represented 
in the references of Stilld's work on Therapeutics, Duboud's Recherches sur les Proprictes Thera- 
petdiques du Seigle Ergote, Paris, 1873, and Husemann's Handbuch der Toxicologic 



OXYTOCICS 



591 



muscles, nausea, giddiness, apathy, with abortion in pregnant women, in suckling 
women drying of the milk, and in maidens amenorrhea. After some time deep, 
heavy, aching pains in the limbs, an intense feeling of coldness, with real coldness 
of the surface, profound apathy, and a sense of utter weariness develop them- 
selves. Then a dark red spot appears on the nose or on one of the extremities; 
all sensation is lost in the affected part; the skin, perhaps over a large surface, 
assumes a livid red hue, and in the foci of local changes bullae filled with serum 
appear. The adynamic symptoms, in severe cases, deepen as the gangrene spreads, 
until finally death puts an end to the scene. Very generally the appetite and diges- 
tion are preserved to the last, and not rarely there is an almost ferocious hunger. 
The gangrene is generally dry, the parts withering and mummifying; but some- 
times it is moist, and pyemic symptoms may even be developed. Of course a very 
large number of cases do not terminate in death; but the part immediately affected 
is generally lost. In these cases the toes most generally are the portion destroyed, 
but it may be any one or all of the extremities; and the nose, lips, ears, and even 
the buttocks sometimes bear t he brunt of the disorder. 

Spasmodic ergotism may in the lightest cases be manifested only by itching, 
formications, numbness, or complete anesthesia of the fingers and toes or of the 
buttocks, and by gastro-intestinal irritation, as shown by colic, vomiting, diarrhoea, 
or constipation, and withal a ravenous hunger. In more severe cases these mani- 
festations are intensified, and spasmodic symptoms appear, violent and painful 
tonic contractions affecting especially the flexors of the extremities, interrupted at 
times by intervals of quiet, but gradually growing into severe general tetanic parox- 
ysms, with opisthotonos and emprosthotonos. In the intervals there are very gen- 
erally muscidar tremblings, and as the case progresses there are developed cerebral 
manifestations, such as disturbances of vision, photophobia, chromopsia, hemiopia, 
and periodic amblyopia and amaurosis, giddiness, cataleptic and epileptic parox- 
ysms with or without loss of consciousness, delirium, and idiocy. Gastro-intestinal 
symptoms are always very marked, but with them are a characteristic ravenous 
hunger and a longing for sour food and drink. The skin is earthy or yellowish 
in tint, and is often spotted with boils or pustules or semi-gangrenous vesicles. 
Death is apparently caused by exhaustion; and in those that recover, various local 
paralyses, habitual spasms, amaurosis, mental aberrations, or even idiocy often 
remain through life. In a few cases the symptoms are still more violent, and the 
spinal and cerebral disturbances soon lead to death. 

The primary changes in ergotism are in the blood-vessels. Ergotic 
gangrene can readily be produced in the comb and tongue of chickens, 
and Von Recklinghausen asserts that the essential lesion in these 
cases is hyaline thrombi in the arterioles and capillaries; while 
Griinfeld has found the walls of the vessels thickened, structurally 
changed, and their lumen occupied by thrombi which in some places 
are full of blood-corpuscles and in other parts undergoing hyaline 
degeneration. 

Administration. — If used in nervous diseases ergot should 
be given in large dose; thus in congestion of the spinal cord we usu- 
ally begin with half an ounce (15 C.c.) of the fiuidextract and increase 
it to an ounce three times a day.* Extract of ergot is preferable to 
the fiuidextract when time is not important, as being less likely to 
cause nausea. When administered by the mouth, it should be given 
in capsules; when used hypodermically, five grains should be dis- 



* It would appear that sometimes, owing to idiosyncrasies, even small amounts of ergot 
cause much disturbance. Thus, R. B. Faulkner reports (New York Med. Journ., June 14, 1884) 
a case in which a fluidrachm of the fiuidextract caused great sleepiness, swelling and redness of 
the feet, and violent prickling of the extremities, probably as the outcome of gastric irritation. 



592 LOCAL REMEDIES 

solved in five minims of glycerin, fifteen minims of boiled water, 
and one-fourth of a minim of phenol, and filtered: the danger of 
causing severe local trouble is lessened by plunging the nozzle of the 
syringe deeply into the muscular tissues. 

The attempt to assay preparations of ergot by their action upon the comb of 
the cock is of doubtful utility; it is at present uncertain whether the action of ergot 
upon the uterus and upon blood-vessels is due to one or to several more or less 
antagonistic substances. 

HYDRASTIS. 

The rhizome and roots of Hydrastis Canadensis, an indigenous 
perennial, commonly known as Golden Seal. Hydrastis contains 
the alkaloid berberine, to which it owes its yellow color, and probably 
also two other alkaloids, canadine * and xanthojmccine, besides its 
characteristic alkaloid, hydrastine.^ The latter occurs in brilliant 
four-sided prisms, inodorous and almost tasteless, but having a very 
bitter and somewhat acrid taste when in the form of a salt. Pure 
hydrastine and its salts can be obtained in the shops, but the 
hydrastm of commerce is an impure body containing berberine, 
hydrastine, and probably other more or less active alkaloids 
besides resin. 

Official Preparations : 

Fluidextractum Hydrastis J to 1 fluidrachm (2-4 C.c). 

Glyceritum Hydrastis i to 1 fluidrachm (2—1 C.c). 

Tinctura Hydrastis (20 per cent.) 1 to 2 fluidrachms (4-8 C.c). 

Hydrastina J to J grain (0.01-0.03 Gm.). 

Physiological Action. — There appear to be no cases on record 
of serious poisoning from any of the alkaloids of hydrastis, and in 
the only case of poisoning by the crude drug, nine grammes of the 
fluidextract produced vomiting, giddiness, headache, dyspnoea; a 
slow, weak, irregular pulse, mydriasis, and hallucinations of sight 
(Friedeberg). The alkaloid hydrastine is so dominant in its action, 
that to it is chiefly due the influence of the crude drug. 

Berberine is an inactive alkaloid, Buchner having taken twenty grains with 
very little effect. In doses of from two to five grains (0.1-0.3 Gm.) it is a simple 
bitter, and as such may be given in pill or alcohol. 

Toxic doses of berberine cause in the lower animals diarrhoea, rapid loss of 
flesh, tremors, diminished respiratory action, progressive paralysis, lessening of the 
pulse-rate, depression of the arterial pressure, partial anesthesia, albuminous or 
bloody urine, and in some cases final convulsions. (Falck and Guenste; Mosse 
and Tautz.) After death hemorrhagic nephritis may be found. Both Schurinow 
and Curci agree that berberine causes the arterial pressure to fall rapidly from 
vaso-motor paralysis; the peripheral vagus is paralyzed. (Schurinow, Marfori, 

* According to the experiments of Bunge, canadine, in toxic doses, produces a brief stage of 
psychical and motor excitability, followed by general paralysis and depression, with death from 
respiratory paralysis, and has little direct action upon the blood-pressure. The rate of pulsation 
in the isolated frog's heart is lessened, but the work done is not decreased by the moderate dose; 
larger doses paralyze the muscle of the heart. The voluntary muscles are not affected by the 
alkaloid, nor is the uterus, although diarrhoea with violent intestinal peristalsis is produced. 

t For an article on the chemical and physiological activities of a number of derivatives from 
hydrastine by Falck, see Virchow's Archiv, 1895, cxlii. 



OXYTOCICS 593 

denied by Curci.) According to Guroi, t ho heart-muscle is directly affected. Schuri- 
iiow and Uosse and Tautz are in accord in asserting that the nerve-trunks arc espe 
eially implicated in (lie poisoning, hut Curci believes that the motor and sensory 
disorders arc due to an action upon the spinal cord; probably both the cord and 
the nerve-trunks are affected. 

Hydrastine causes, in animals, increased, followed after a time by 
lessened, respiratory movements, salivation, vomiting, excessive peri- 
stalsis, muscular tremblings, weakness and rigidity, loss of voluntary 
movement, rise of bodily temperature (Bunge) (often followed by a 
falO, feeble, rapid pulse, clonic and tetanic convulsions, increased 
reflex activity, and death from cramp-asphyxia or general paralysis, 
or exhaustion with respiratory failure. Hydrastine is probably 
eliminated through the kidneys. (See Phillips and Pembrey.) 

In a research upon the effect on the lower animals of the long-continued use 
of hydrastine and hydrastinine, J. De Vos found that these alkaloids have no cumu- 
lative action, but that gradually the animals seem to become accustomed to their 
use. Neither of them in any way disturbed the gastric or intestinal digestion. 
Albuminuria never occurred, nor was there apparent disturbance of assimilation. 

Nervous System. — So far as is known, hydrastine has little or no 
action upon the cerebral hemispheres, but is a powerful stimulant 
to the motor side of the spinal cord. Death may occur during the 
period of violent convulsions with heightened reflex activity; but if 
the animal survives, there follows a general paralysis, which, as the 
alkaloid is a marked depressant to the motor nerve-trunks, is 
probably of peripheral origin. 

According to Cerna, when voluntary movements and the reflexes are first 
depressed in the frog, the reflexes can be restored by section of the cord, so that the 
palsy is probably due to stimulation of Setschenow's centre; later it is irremediable. 
Late in a protracted poisoning, and after death, the motor nerves are depressed or 
altogether paralyzed (Falck, Cerna), and Bunge has found that the local appli- 
cation of a solution of the alkaloid to a nerve kills it. According to Falck, hydras- 
tine placed in the eye has no effect upon the sensitiveness of the conjunctiva, but 
both Slavatinski (quoted by Bunge) and Mays affirm that late in the poisoning 
there is general loss of sensibility. Mays further states that when brought in con- 
tact with a nerve-trunk, hydrastine paralyzes its sensory fibres, although tying an 
artery does not prevent the development of anesthesia in general poisoning by the 
alkaloid. If these experiments be correct, the alkaloid acts both upon the sensory 
cord and sensory nerve; this action, however, is entirely subordinate to its influence 
upon the motor tract. 

Muscles. — Upon the muscles the alkaloid has some influence, 
since both Falck and Bunge have found that its not too dilute solu- 
tion directly applied to a muscle destroys its contractile power, a 
conclusion which is confirmed by Cerna, who further states that 
preceding the depression there is a stage of excitation in which the 
muscular contraction under stimuli is more complete and prolonged 
than normal. 

Respiration. — When death takes place during a convulsion, it 
probably is due to cramp-asphyxia; but when it occurs during the 
38 



594 LOCAL REMEDIES 

paralytic stage, it is from paralytic-asphyxia (probably, in part at 
least, of centric origin), the heart-beat continuing after death (Serdzeff). 
Circulation. — The characteristic primary effect of a full dose of 
hydrastine upon the circulation is a rise of the arterial pressure with 
slowing of the pulse-rate, this condition being followed after a time, 
if the dose has been toxic, by a fall of the arterial pressure. The rise 
of the arterial pressure is probably due in part to a direct action upon 
the heart itself and in part the result of contraction of the blood-vessels, 
caused probably by an action upon their muscle-fibres. Marfori 
believes that the vaso-motor centres are also stimulated, but at present 
this is only a probability. The fall of the arterial pressure is in part 
of cardiac origin, there being in the later stages of the poisoning a 
depression of the heart muscle, which ends in diastolic arrest with 
loss of muscular irritability. 

Although W. W. Williams failed to obtain any but the most insignificant rise 
in blood-pressure from hydrastis the observations of Bartholow, Fellner Falck, 
Marfori and Pellacani would seem to establish that, — when hydrastine in sufficient 
dose is injected directly into the circulation there is an immediate fall of pressure, 
followed by a marked and long-continuing rise unless the original dose has been 
excessively large, when the pressure falls progressively until death. The primary 
fall of pressure does not occur after subcutaneous injections (Falck), and is due to 
direct action of the concentrated drug upon the heart. That the rise of pressure is 
partly of cardiac origin is proven by the following facts: Marfori, also Phillips and 
Pembrey, have noted that when hydrastine is applied to the isolated frog's heart 
it produces slowing of the rate with increased amplitude and power of the cardiac 
beat, and Serdzeff has proven an actual increase in the work of the isolated heart. 
Further, the rise of the arterial pressure is not prevented in the mammal by previ- 
ous section of the splanchnic nerve or of the spinal cord high up (Fellner). Again, 
Cerna found that the slow pulse of the hydrastine-poisoning occurs after section of 
the pneumogastric nerve; also, that the vagi nerves retain their power up to the 
fatal issue; the slow pulse, therefore, is not of inhibitory origin. That the vessels 
are contracted is indicated by the oncometrical experiments made by Marfori upon 
the dog's kidney, in which the contraction of that organ was found to be a constant 
phenomenon of the early stages of hydrastine-poisoning. 

It is probable that both voluntary and involuntary muscle-fibres 
show the primary stimulating influence and the later depressing 
power of hydrastine, and that the action of the drug upon the circu- 
lation is the same as that upon the uterus and the voluntary muscles, 
only that the voluntary muscle-fibres are less susceptible to its action 
than are those of involuntary life. 

Abdominal Action. — It is probable that hydrastine influences 
both the glands and muscular fibres of the alimentary canal. Accord- 
ing to Cerna, it markedly increases the secretion of saliva and of bile, 
also the intestinal peristalsis. 

Uterus. — As long ago as 1883 Schatz called attention to the prac- 
tical value of hydrastis in all forms of hemorrhage from the womb. 
As the result of experiments upon the lower animals, both Fellner 
and Slavatinski affirm that hydrastine has a distinct ecbolic action, 
causing uterine contractions in the non-pregnant uterus and abortion 
in pregnant rabbits. Slavatinski reports a case of premature labor 



OXYTOCICS 



595 



produced by hypodermic injections of two or three grammes repeated 
daily. It would seem, therefore, that hydrastine is an ecbolic", and 
that it arrests uterine hemorrhage in part, if not altogether, by 
provoking muscular contractions. 

Eyes. — Hydrastine locally applied to the eye causes at first 
contraction and afterwards dilatation of the pupil (Cerna). 

Absorption and Elimination. — Hydrastine appears to be absorbed 
from the alimentary canal somewhat slowly; at least it is stated by 
Bunge that ten times as much of it is required to kill an animal when 
given by the mouth as when injected hypodermically. Marfori 
states that it is apt to have a cumulative action when given for a 
length of time. It escapes unchanged through the kidneys, and has 
also been found bv Hirschhausen in the feces. 



SUMMARY. — Hydrastis is a powerful stimulant to the spinal 
cord, -which in toxic doses is secondarily depressant. The final 
paralysis is also, at least in part, the outcome of depression of the 
motor nerves and also of the muscles themselves. The arterial 
pressure is first elevated and secondarily depressed : the first rise 
of pressure is probably due to the stimulation of the heart-muscle, 
increasing the output of force, and of both the vaso-motor centres 
and the muscle-fibres in the arteriole coats, causing contraction of 
the blood-vessels : the fall of pressure is the result of a direct para- 
lytic action exerted upon the muscle-fibres in the heart and in the 
arterioles. Hydrastine notably increases intestinal peristalsis, and 
probably uterine contractions. It would seem to be a universal 
muscle-poison, which acts upon both striated and non-striated 
muscle-fibres in the heart, arterioles, intestines, uterus, and gener- 
ally throughout the body ; its first stimulant action being followed 
by marked depression. 

Therapeutics. — When locally applied, the preparations of hy- 
drastis have a very remarkable effect upon the mucous membranes. 
They have been used with asserted excellent results in chronic gastro- 
intestinal catarrhs, especially those due to alcoholic excesses. In the 
second stages of gonorrhoea, after the acute inflammation has been 
subdued, injections of hydrastin, or the fluidextract, suspended in 
mucilage, are often of service; ten to twenty minims of the fluid- 
extract may be used to the ounce of fluid. It is also asserted by 
various specialists that in otorrhea, nasal, vaginal, and other mucous 
catarrhs the remedy is locally of great value. In dyspepsia it has 
been used as a stomachic stimulant, and has received especial praise 
in the vomiting of pregnancy. At present it is not known to which 
of the various ingredients of hydrastis these local effects are chiefly 
due, so that a preparation of 'hydrastis is preferable to the pure 
alkaloid. 

Hydrastis has been used to a considerable extent, with asserted 
good results, in various uterine fibroids, menorrhagia and various 
forms of hemorrhage from the womb. For internal or general medica- 
tion, as contrasted with the local use of hydrastis, the alkaloid or its 



596 LOCAL REMEDIES 

salts is much preferable to the cruder preparation. As anti-hemor- 
rhagic or ecbolic, the alkaloid hydrastine may be used in doses of from 
one-sixth to one-half grain (0.01-0.03 Gm.). 

HYDRASTININE HYDROCHLORIDE. 

Hydrastinine is an artificial alkaloid first produced by Martin 
Freund by the oxidation of hydrastine. The hydrochloride is a light 
yellow crystalline powder, somewhat deliquescent, odorless, having a 
bitter saline taste, soluble in 0.3 part water and three parts alcohol. 

Hydrastininse Hydrochloridum J to 1\ grains (0.0.5-0.1 Gm.). 

Absorption. — Bunge has found that hydrastinine is readily 
absorbed and eliminated unchanged, chiefly with the urine, but also 
to some extent with the saliva, bile, and intestinal secretions. It 
did not appear to increase the amount of bile secreted. 

Physiological Action. — In mammals hydrastis causes hyper- 
esthesia, general tremors, rapid pulse, and dyspnoea, followed by 
paresis, which is said primarily to affect the front legs and to pass 
into general paralysis with dilated pupils, lowered temperature, and 
death from failure of respiration. According to Bunge, intestinal 
peristalsis is markedly increased by hydrastinine. 

Nervous System. — Hydrastinine is a depressant to the psycho- 
motor area in the brain and also to the motor ganglia in the spinal 
cord. It also probably lessens the irritability of the peripheral 
motor nerves and voluntary muscles. 

It has been found by W. Kiselew that the excitability of the motor cerebral 
cortex progressively decreases with progressively increasing doses of hydrastinine, 
although it never entirely disappears; and that the white substance of the brain is 
affected similarly to but less powerfully than the gray matter. Kiselew has also 
confirmed the previous observation of Tarchanoff , that the alkaloid arrests or greatly 
diminishes the convulsive attacks in epileptic guinea-pigs. It is further worthy of 
remark that Kiselew, in a few cases of human epilepsy, obtained favorable results 
from the administration of 0.01 to 0.03 gramme of hydrastinine four times a day. 

It seems at present doubtful whether there is or is not an early stage of spinal 
excitement, since Archangelsky affirms that there is increase of susceptibility to 
touch and to pain in the frog after small doses, while Marfori states that there is no 
increase of the reflex activity at any time. If there be any stage of excitement, it 
cannot be well pronounced. It is affirmed that hydrastinine is the natural antag- 
onist of strychnine, and Marfori asserts that the paralysis is of purely central origin. 
This, however, seems to be incorrect, for not only, as Archangelsky found, is the 
excitability of the voluntary muscle lessened by the toxic dose of the alkaloid, but 
Bunge has shown that both the peripheral nerves and the muscle-fibres were 
paralyzed by a local application of the hydrastinine solution. 

In the advanced poisoning the respiratory centre seems to show the depressing 
influence of the alkaloid, and hence respiratory failure; but here again, according 
to Archangelsky, especially when the dose has not been too large, there is a period 
of primary centric stimulation. 

Circulation. — All observers are in accord in stating that the blood- 
pressure is increased by the large dose of the alkaloid. The increase 
appears to be in part of cardiac and in part of vascular origin. 



OXYTOCICS 597 

Both Marfori and Bunge, in experiments made with the Williams apparatus, 
[bund that the systolic impulse of the isolated frog's heart becomes abnormally 
strong under the influence of the drug, and that the amount of the heart's work is 
distinctly increased. \V. \Y. Williams concludes, from rather insufficient experi- 
mental data, that the rise of pressure from hydrastinine is chiefly of cardiac origin. 
But there is evidence thai there occurs also a contraction of the vessels, which, 
according to Marfori, may become so great as entirely to arrest the renal secretion. 
As the result of elaborate experiments made with section of the splanchnics and of 
the spinal cord, Archangelsky reaches the conclusion that the contraction of the 
vessels is chiefly of peripheral origin,* although there is at the same time some 
stimulation of the vaso-inotor centres in the medulla, — a conclusion concordant 
with Marfori's results. 

When the amount of the hydrastinine has not been too large, the elevated arte- 
rial pressure gradually returns to the normal (Bunge); but after a fatal dose of the 
alkaloid a pronounced fall of pressure finally comes on, apparently as the result 
of the paralysis of progressive asphyxia, since artificial respiration will bring back 
the pressure to the normal (Marfori): further, it is asserted by various observers 
that the heart is finally arrested in systole, so that it would seem that hydrastinine 
differs from hydrastine in not being a cardiac paralyzant in any dose. 

Pupils. — Archangelsky has noted that one to two drops of the 
ten-per-cent. solution of a salt of hydrastinine in the eye will produce 
a dilatation of the pupil, which reaches its maximum in two to three 
hours, and remains twelve to fifteen hours. 

Uterus. — The effect of hydrastinine upon the uterus was studied 
in pregnant and puerperal dogs, cats, and rats by Archangelsky, who 
found that it produced rhythmic contractions, independent of any 
vaso-motor influences, apparently by stimulation of the uterine 
walls. On the other hand, Bunge, having failed in two experiments 
to provoke abortion or uterine contractions in pregnant animals by 
large or even fatal doses of the alkaloid, affirms that it is not an 
ecbolic. Nevertheless, Faber, as the result of a number of trials, states 
that hydrastinine given hypodermically during human labor very 
notably increases the force and length of the uterine contractions, 
^ausing a spasm which affects all portions of the uterus, and which 
is similar in character to that provoked by ergot. In some of the 
cases there was uterine tetanus, lasting as long as fifteen minutes. 
Faber also asserts that distinct contractions can be produced in the 
unimpregnated womb. 

Therapeutics. — Hydrastinine is used in medicine chiefly for 
those complaints for which it was originally recommended by Falck, 
— namely, menorrhagia, metrorrhagia, congestive dysmenorrhea , and 
even endometritis. The testimony in favor of its arresting uterine 
hemorrhage in all forms is, on the whole, very consistent, and is 
abundant, but it is also believed by many gynecologists to have some 
alterative influence upon the mucous membrane of the uterus. It 
is affirmed by some gynecologists, but denied by others, that it is 
an active oxytocic, and exerts its influence upon impregnated and 

* The assertion of Bunge, that because in heavily chloralized animals hydrastinine fails to 
elevate the pressure, therefore it acts chiefly upon the vaso-motor centre, is a non sequitur, as 
chloral acts upon the whole circulatory apparatus. Moreover, Bunge's own experiments show 
that the alkaloid lessens the size of the spleen by contracting the blood-vessels. 



598 LOCAL REMEDIES 

unimpregnated wombs largely by causing muscular contractions. 
It will be seen that the range of its usefulness in gynecology is entirely 
similar to that of hydrastine; it has, however, acquired popular 
favor more rapidly and decidedly than the natural alkaloid. It may 
possibly be more effective as an ecbolic, but its superiority probably 
lies in chief part in its being distinctly less toxic and producing cardiac 
stimulation rather than cardiac depression. When an immediate 
impression is desired, the sulphate should be given hypodermically. 
When a prolonged continuous action is required, it may be admin- 
istered by the mouth. The results obtained by Kiselew demand a 
fair trial of it in epilepsy. Hydrastinine has some value as a sub- 
sidiary cardiac tonic; it does not belong in the same class as digitalis, 
but its tonic influence is often decidedly helped by its cardiac action. 

Gossypii Cortex. — The root of the ordinary cotton-plant, the Gossypium 
herbaceum and other cultivated species of Gossypium, is said to be used by the 
negroes in various portions of the South as an abortifacient, and Bouchelle, as long 
ago as 1841, affirmed that it has medical properties similar to those of ergot. It 
has not, however, come into general use, and our knowledge of its properties is very 
scanty and uncertain. In the experiments of I. C. Martin enormous doses produced 
heaviness and stupor in both frogs and mammals, but did not cause abortion in 
pregnant guinea-pigs or rabbits: On the contrary, Mohr produced abortion in a 
cat with three doses of 20 C.c. each of the fluidextract. H. I. Garrigues lias found 
cotton-root a serviceable agent in arresting hemorrhage and ameliorating the other 
symptoms of uterine polypoid and fibroid tumors, and even of uterine cancer. He 
insists that the commercial fluidextract is inert and the decoction must be freshly 
prepared. The oxytocic dose of a decoction (four ounces in a quart of water boiled 
to a pint) is stated to be a wineglassful, to be repeated every thirty minutes as neces- 
sary. The remedy has also been employed in amenorrhaea and in dysmenorrluea, in 
which diseases from three to five grains of a solid aqueous extract have been given 
three times a day. The fluidextract may be used in doses of a fluidrachm (4 C.c). 
Absorbent Cotton (Gossypium Purificattjm) is ordinary cotton wool deprived of 
impurities and fatty matters. It is used mechanically, and as an absorbent. 



REFERENCES. 



ERGOT. Kelly Med. Register, 1887. 

t. jo- t> n m i ■•• -o. Kersch Betz's Memorabilien, xviii. 

Bailly and See. .B. G. T lxxvm. 435 Kobeht A. E. P. P.. 1884, xviii. 316. 

Barker and Dale. .Biocnem. Journ., 190,, u. Kohler and Eberty. . V. A. P. A., lx. 384. 

24 r °- , „ . „ , LeGendre B. G. T.. lxxvii. 282. 

Barlan-Fontayral. .Journ. des Sci. Med. Luton G H M C Oct 1871 

pratiques de Montpellier, Meadows! '.'.'.'.'.'. !Pract\, i." 166. 

vi.; vii. Meltzer and Auer. .A. J. P., xvii. 143. 

Bodin Journ. des Connaissances Neubert Journ. f. Pharmacodyn.. 

Med., 1842. 1860 ii 483 

Boldt S. Jb., March 1872. Oldright Canada Med. Journ., 1850, 

Boreischa Arb. Pharmak. Lab. Mos- 494. 

„ „. , ka i U ' i' 5 ?o-r> ••• Ar,A Peton De l'Action de l'Ergot, 

Brown-Sequard .A. de P., 18,0, 111. 434. Paris 1878 

Da Costa A. J. M. S., Jan. 1875. Plumier J. de P. P., 1905, vii. 13. 

D AVIS ii '■ , \. •', 18 ° 4 - „„ Poyet and Oommarmond. .Ann. de la Soc. de 

Dehenne Munich Med., xlv 86. Med. de Saint-Etienne et 

Eberty £»■ D 's ; . Halle, 18, 3 de j a Loire, 1863. 

Goodeli Proc - Med. Soc. of Pennsyl- Ri NGER a nd Sainsbury. . B. M. J., Jan., 1884. 

_, .. T v ^" ia . I 8 ' 3 - ,„„„ Schuller B. K. W., 1874, 304. 

Grunfeld J n - T P ls -, Dorpat, 1892. Sollmann and Brown . . J. A. M. A., 1905, xlv. 

Haudelin S. Jb., civ. 2 9 9 

Hemmeter M. News, 1891, lvii. Sunoi L. M.R., 1884. 

Heusinger Journ. fur Pharmakod., i. Tardieu An. d'H., 1855, i. 

405. Tulasne Ann. des Sciences Nat., 

Hildebrandt . ...B. K. W., June 17, 1872. Botan., 1853, 3 s., xx. 

Holmes A. de P., 1870, iii. Vahlen A. E. P. P., lv. 1906, 1 16. 

Jacobi A. E. P. P., 1897, xxxix. 85. Vogt B. K. W., 1869, No. 12. 



OXYTOCICS 



599 



REFERENCES (Continued) 



\\ t BNICB V. \. P. \.. 1872, hi. 610. 

WnunviMH! hihI Maomn A. • It- 1'., 1892, 
:. -. iv. D2. 

Wooi. P. M. T. 1874 iv. MS. 

Wui.aiT Ed. M. S. J., Oot. 1839. lii. 

HYDRASTIS. 

Bartiioi.ow Lloyd's Drugs and Med. of 

North America. 

Cl una T. (!.. 1891. 

Cnaci I.. M. K., Oct. 11, 18S6. 

De Vos IVessc M. H., 1895, xlvii. 

Kaiser Tli. M., 1892, vii. 

FALCK and GcENSTE V. A. P. A., 1890, cxix. 

Fkllnbb Wien. Med. Jahrb., 1885. 

Friedeberq S. Jb., cclxviii. 

MOSSE and Tactz.Z. K. M., xliii. 



Phillips and Pbmbrey..J. P., 1897, xxi. 

liu rHEKFORD B. M. J., 1879, i.; ii. 

SbRDZBPF In. Dis., Moscow, 1890. 

\\ [LLIAMa J. A. M. A. 1908, 1.26. 

HYDRASTININB. 

Bunqb In. Dis., Dorpat, 1893. 

KlBELBW S. Jb., ccxxxviii. 

M wii'om A. E. P., P. xxvii. 

Williams J. A. M. A., 1908, 1. 29. 

GOSSYPII CORTEX. 

G armours Quart. Bull. Clin. Soc, N. Y., 

Jan., 1887. 

Martin A. J. M. 3., Jan., 1882. 

Mohr Ther. Geg., 1905, vii., 300. 



FAMILY IX.— IRRITANTS AND COUNTER- 
IRRITANTS. 



IRRITANTS. 



In the treatment of diseases of the skin various irritating sub- 
stances are used for the purpose of stimulating the nutritive activity 
of the diseased part. The most important of these drugs are noticed 
at this place. 

Soap. — Under the name of Sapo the U. S. Pharmacopoeia recog- 
nizes ordinary white castile soap, a combination made between olive 
oil and soda, and consisting chiefly of a mixture of sodium oleate 
and palmitate. This soap is entirely free from irritant properties, 
and is used externally as a detergent and sometimes internally in 
combination with laxatives to render their action milder and perhaps 
more effective. 

Soft Soap (Sapo Mollis) or Green soap, as it was formerly called, 
is made by the action of potassium hydroxide upon linseed oil; more 
potash being used than is necessary for the neutralization of the 
fatty acids, so that the resulting combination is not only strongly de- 
tergent but also irritant, and even mildly caustic. Formerly, when 
vegetable oils contained much chlorophyll, this soap had a distinct 
greenish color, but as now prepared it is a brownish or yellowish 
semifluid mass, which yields a nearly clear solution with five times 
its weight of hot water. It is used chiefly in the treatment of eczema. 
It destroys fatty matter rapidly, softens down exudation, and 
markedly affects the nutrition of the skin. 

Chrysarobin. — Under the name of Goa Powder, Araroba or 
Chrysaroba, certain powders varying from fine to coarse and from 
light yellow to dark chocolate, have long been used in Brazil and the 
East Indies. Formerly supposed to be the product of certain lichens, 
they are now known to be obtained from irregular interspaces in the 
wood of the Andira Araroba, a large Brazilian tree. Goa powder 
depends for its activity upon chrysarobin. The percentage of chrys- 
arobin in the goa powder varies so much that the crude drug is not 
recognized in the U. S. Pharmacopoeia. 

Chrysarobin * is an odorless, tasteless powder, when first obtained 
of a pale orange color, but darkening on exposure. It is very slightly 

* Chrysarobin must not be confounded with anthrarobin, a distinct substance produced by 
Liebermarin from alizarin (Ber. d. Chem. Ges., 1888), which Weyl (Arch. f. d. Ges. Phys., 1888, 
xliii.) has proved to be free from poisonous properties. 

600 



COUNTER-IRRITANTS 601 

soluble in cold water or alcohol, but is freely soluble in alkaline 
solutions and in hot fats; formerly supposed to be identical with 
ohrysophanic acid, ehrysarobin is now known to he a distinct neutral 
principle. When taken internally in doses of from six to eight grains, 
it produces in about four hours repeated vomiting, sometimes fol- 
lowed by purging (I. A. Thompson), and it has been shown by Weyl 
to be an active irritant poison. 

Unguent urn Ohrysarobin (6 per cent.) External use. 

Chrysarobin is never used internally, but as a local application 
in various skin diseases when there is a tendency to excess of dry 
exudation, being especially effective in psoriasis. 

COUNTER-IRRITANTS. 

Almost from time immemorial physicians have believed that 
morbid processes in deep-seated or superficial organs could be modified 
by irritations artificially induced in distant parts. To the drugs 
used for producing these remedial irritations the name of revulsants, 
or counter-irritants, has been given, the process being called revul- 
sion, or counter-irritation. 

The question as to the manner in which a counter-irritant acts is 
essentially distinct from the question whether it does or does not act. 
However crude and uncertain our theories may be, clinical experience 
has demonstrated the value of counter-irritants in various internal 
conditions. It is proved beyond cavil that internal morbid processes 
may at times be relieved by creating external irritations. 

Our present explanations of the way in which counter-irritants 
act are certainly not satisfactory. There are abundant physiological 
proofs demonstrating the connection between distant organs having 
no apparent anatomical connections; such is the relation between 
the mammary glands and the uterus; such are the phenomena of 
so-called metastasis seen in mumps, gout, and other constitutional 
disorders, in which the development of a new irritation is accom- 
panied by the disappearance of one already existing. Familiar exam- 
ples, also, may be found in the paraplegias sometimes produced by 
irritation of a renal calculus, in the headache of gastric irritation, 
in the shoulder-pain of diseased liver, and in the amaurosis or epilep- 
tiform attacks sometimes caused by a decayed tooth. In the well- 
known experiment of Brown-Sequard it was found that if one sciatic 
nerve of the guinea-pig be cut epileptic attacks may be produced 
by gently rubbing the back of the ear upon the same side. 

One commonly offered explanation of counter-irritation is that 
there is only a certain amount of blood in the body, and that if the 
blood be drawn to one part there must be less in another part. Surely, 
however, the amount of blood drawn to the skin by a mustard plaster 
is too small sensibly to affect the general mass in the body. It is 
more probable that the phenomena of counter-irritation are the 



602 LOCAL REMEDIES 

result of reflex disturbances of the vaso-motor nerves which influence 
the size of the blood-vessels, or of the trophic nerves which directly 
affect nutrition. 

It is of great practical importance to know where the counter- 
irritant should be placed to affect most powerfully any given internal 
organ. We have no thoroughly scientific experimental knowledge 
as to this matter, but it has been clinically demonstrated that the 
general law for deep-seated parts is that the revulsant should be put 
directly over the part. When a superficial action is desired, other 
directions are needed. We are indebted to Anstie for pointing out 
what appears to be a law, or at least a good working rule for prac- 
tice, — namely, that when a superficial part supplied by the anterior 
branches of a spinal nerve is to be affected, the counter-irritant should 
be placed over the posterior roots of the nerve. Not only can obsti- 
nate neuralgia often be relieved by this reflex action, but also the 
inflammatory changes so often coincident with intercostal neuralgia. 
The law seems also to apply to cervical nerves, since the proper posi- 
tion for the blister in trigeminal neuralgia is back of the ear or on the 
nape of the neck.* 

For the purposes of study, counter-irritants are conveniently 
arranged under two heads: first, those which do not provoke decided 
alterations of the dermal structure, but simply cause an irritation 
which soon passes away; these are the Rubefacients: second, counter- 
irritants which produce severe structural alterations. In the latter 
class belong the hot iron, the issue, the seton, and other destructive 
appliances, and also the epispastics, vesicatories, or more colloquially 
blisters, which are used to produce that peculiar inflammation of the 
cuticle with an outpouring of serum commonly known as the blister. 

In choosing between a rubefacient and a blister, the physician is 
guided by the character of the disease present in the subject. A rube- 
facient causes a wide-spread, intense but temporary, irritation and 
congestion of the part, — an irritation which for the moment produces 
a strong influence, but leaves no permanent impression upon the nutri- 
tive acts of the diseased organ. A rubefacient is to be employed 
when the disease is functional, — when there is only a nervous disturb- 
ance or a congestion to be dealt with; whereas the blister is useful 
when inflammation has produced permanent change. Very frequently 
in inflammatory conditions, however, rubefacients are useful to 
relieve accompanying congestion. Thus, in a pneumonia the rube- 
facient may have no effect upon the focus of the disease, but may 
be very serviceable in checking a wide-spread collateral congestion. 
To the careful use of rubefacients there are scarcely any contra- 
indications; some caution is, however, necessary in their application. 
A severe internal irritation may so successfully counter-irritate against 

* The statement of A. Dumontpallier {Gaz. Hebdomadaire, November, 1879), that the best 
results of counter-irritation are obtained by applying the counter-irritant upon the opposite side 
of the body, so as to be exactly symmetrical with the diseased part, has never to our knowldege 
been confirmed. 



COUNTER-IRRITANTS 603 

the externa) counter-irritation that the hitter has for the time being 
no apparent effect, ami yet really exerts a disorganizing inlluenee. 
Thus, a mustard plaster, under the circumstances named, may at 
the time of its application produce no pain or redness, and yet twenty- 
four hours afterwards disorganizing inflammation may set in at the 
seat of the application. When there is severe internal irritation the 
counter-irritant should always be removed when it has been applied 
long enough to endanger violent local effects, even though it has 
exerted no sensible influence. 

There is one use of rubefacients which is not that of counter- 
irritation, but which is often of practical importance. An irritation 
of the sensitive nerve in the normal animal produces an immediate 
vaso-motor spasm, and in certain conditions of the body irritation 
of the mucous membrane or of the skin is of great service in stimulat- 
ing respiration or circulation. In a true exhaustion rubefacients 
are of very little value, for the only possible source of absolute in- 
crease of power to the system is in food; and in exhaustion those 
stimulants should be employed which increase the power of assimi- 
lating food. For this reason, external irritants are useful as stimulants 
in conditions of depression rather than of exhaustion. Especially 
are they valuable when there is wide-spread loss of functional activity 
in the vaso-motor system. Such conditions of depression, with vaso- 
motor weakness, exist in acute collapse from any cause, in shock fol- 
lowing injuries, in the first stage of pernicious malarial fever, and in 
other cases when the powers of the system are seemingly overwhelmed 
by some depressing agency. 

Blisters are especially useful in inflammations of serous membranes, 
such as pleuritis and peritonitis; are very strongly recommended by 
some practitioners in parenchymatous inflammations, such as pneu- 
monia; and may be of service in persistent forms of nervous irrita- 
tion, such as the maniacal delirium of fevers, when dependent upon 
the irritant action of a blood-poison, and not upon exhaustion. The 
amount of serum which is poured out from a blister is sometimes 
quite large, and vesicants have been even employed to relieve dropsy. 
In general dropsy their use is simply unjustifiable; but in local drop- 
sies, as, for example, serous effusion into the pleural sac or into the 
pericardium, dependent upon local inflammation, they often do good, 
not only by affecting favorably the disease-process, but also by 
hastening the removal of the effusion. 

In some chronic affections, long-continued severe counter-irrita- 
tion is required: in such cases a blister may be "kept open" by the 
use of stimulating ointments, such as the mezereon ointment. In 
chronic inflammation of the joints, repeated blistering is very often 
of service. When the inflammatory action is rheumatic, in our experi- 
ence better results are obtained by repeated blistering than by 
keeping a blister sore by means of irritants. In neuritis, whether 
rheumatic or otherwise, blisters are often of service: they should 
be applied as a long narrow strip along the course of the nerve. In 



604 LOCAL REMEDIES 

obstinate local neuralgia, very mild blistering over the seat of pain, 
or in accordance with Anstie's law, is sometimes found to be 
advantageous. 

The contraindications to the use of blisters are high arterial and 
febrile excitement and a decided want of vital power. In the former 
case, the irritating influence which they exert upon the general system 
may increase the constitutional disturbance to such an extent as to 
do more injury than any local benefit derived from them can do 
good. When the vitality is very low, blisters may give rise to slough- 
ing ulcers, which, refusing to heal, may waste very seriously the already 
exhausted system. Hence, in all acute diseases of such type that the 
nutritive forces are exceedingly depressed, blisters must be avoided, 
or be used only with great caution. For the same reason, great care 
must be exercised in their employment in the very young or the very 
aged. Very rarely indeed is a blister called for in the case of a young 
infant, and if it be employed at all, it should be allowed to remain in 
contact with the skin only long enough to produce slight pain or 
redness, and the complete vesication should be obtained by the after- 
use of a poultice. 

The hot iron or other destructive counter-irritant is to be used only 
in cases of continuing chronic disease with structural lesion. At 
present, neither the moxa nor the issue is ever employed in civilized 
countries; the seton with extreme rareness. The actual cautery, 
however, affords a valuable method of treating chronic neuritis, 
chronic meningitis, cerebral or spinal, and various forms of chronic 
arthritis. 

EPISPASTICS. 

There are various substances which are capable of producing 
vesication, but the only one in ordinary use is cantharides. In cases 
of emergency ammonia is sometimes employed. (See page 185.) 

CANTHARIDES. 

The dried bodies of the Cantharis vesicatoria. a beetle inhabiting 
Southern Europe. Spanish flies are from half an inch to nearly an 
inch in length and two to three fines in breadth, and have a large 
heart-shaped head and brilliant metallic-green elytra, or wing-cases 
Their odor during life is very strong and fetid, but is almost entirely 
lost in drying; their taste is urinous, very burning, and acrid. When 
ground, Spanish flies afford a grayish-brown powder, full of minute 
greenish spangles, the remains of the feet, head, and wing-cases. 
The active principle of cantharides is cantharidin, which occurs in 
white crystalline scales, is inodorous, tasteless, insoluble in water, 
nearly so in cold alcohol; soluble in ether, benzole, the oils, and also 
very freely so in chloroform. Notwithstanding the insolubility of 
pure cantharidin, Spanish flies yield their virtues to alcohol and 
to water. 



COUNTER-IRRITANTS (i()f> 

Official Preparations: 

Ceratum Gantharidia External use. 

Colkxliuni Cantharidatum External use. 

Tinctura Cantharidis (10 per cent.) 1 to 2 minims (0.06-0.12 C.C.). 

The plaster although not official is the most popular preparation for external use. 

/.<)(•(// Action. -Absorption and Elimination. — Cantharides is very 
irritating, and. when applied to the skin, causes at first redness, with 
burning, then free vesication and severe pain, and, if the contact be 
longer maintained, deep inflammation and sloughing. Upon the 
mucous membranes it produces a no less intense effect. The can- 
tharidin is rapidly absorbed, and is eliminated unchanged by the 
kidneys. 

Therapeutics. — Cantharides is employed internally as a stimulant 
to the genito-urinary organs in chronic inflammation and in amen- 
orrhea. When cantharides is freely used externally as a vesicant 
there is always some danger of the absorption of a sufficient amount 
of the active principle for strangury to be induced. The blister should 
therefore not be left on longer than is absolutely necessary, and in 
susceptible persons care has to be exercised in its use: whenever 
active irritation of the kidneys exists, cantharidal blisters should not 
be applied.* 

Toxicology. — Toxic dose of cantharides produces in a few 
minutes a burning pain in the pharynx, oesophagus, and a sense of 
stricture in the throat, soon followed by epigastric pain and vomiting, 
and later, in the majority of cases, by purging. The matters vomited 
are at first mucus, showing, if the drug has been taken in a powder, 
little greenish specks through them; then bilious and finally bloody. 
The stools are mucous, then fibrinous and bloody, often very scanty 
but excessively numerous and their passage accompanied by great 
tenesmus. In most cases severe salivation is developed earty in the 
poisoning, frequently accompanied by great swelling of the salivary 
glands, burning pain in the genito-urinary tract with complete stran- 
gury as a characteristic symptom of the poisoning. Aching pain in 
the back and frequent micturition indicate a commencing uro-genital 
irritation. These symptoms increase in intensity until there is a 
constant, irresistible desire to urinate, with violent tenesmus of the 
bladder, and yet an inability to pass more than a few drops of urine, 
which is albuminous, and not rarely bloody. In some cases there is 
a violent erotic excitement, an unquenchable lust, accompanied in 
man by numerous seminal emissions; f violent priapism, swelling 
and heat of the organs, and even severe inflammation of the parts 
may indicate the intensity of the local action of the poison; sometimes 
gangrene ultimately occurs. Consciousness and general power are 
often long preserved when the local symptoms and agony are intense, 

* In 1891 Liebreich advocated the use of cantharidin salts in lupus, phthisis and other forms 
of tubercular disease. His theory of their action was, however, very improbable, and the method 
has so entirely failed in practice that it is not necessary here to do more than refer the curious 
reader to the tenth edition of this treatise for information concerning it. 

t Cases, Journ. de Pharm. el de Chimie, June, 1871. 



600 LOCAL REMEDIES 

but, if the dose have been large enough, sooner or later collapse comes 
on, with the usual accompaniments, and the prostration deepens into 
complete powerlessness, stupor, coma, and finally death. In some 
cases violent hydrophobic delirium and severe tetanic convulsions 
are said to have occurred (Tardieu). Paraplegia has been noticed 
in several cases by Palle: it was probably reflex in its origin, and due 
to the intense irritation of the genito-urinary organs. 

In animals, cantharides produces very much the same symptoms as it does in 
man. In dogs, according to the experiments of Orfila and of Beaupoil, the symptoms 
of gastro-intestinal inflammation are more prominent tlian those of irritation of the 
genito-urinary tract. It has been asserted tliat the lack of erotic excitement in 
these cases shows that the medicine acts differently upon man and upon animals. 
As already stated, however, erotic delirium is very often absent in fatal poisoning 
in man, while SchrorT states that ten drops of the tincture of cantharides will fre- 
quently produce great sexual excitement in man, and the whole drift of the evidence 
is that libidinous desires are much more likely to be caused by amounts of Spanish 
flies but slightly toxic than by fatal doses. Indeed, the irritation caused by the 
latter would seem to be too intense, the general perturbation too great, for erotism 
to be induced. There appear to be the same differences in the effects of different 
doses of the drug upon animals. Fatal doses very generally do not excite sexual 
desire; but Schubarth (quoted by Stille) found that small doses do cause evident 
salaciousness and irritation of the genital organs, while, according to Husemann, 
the peasants of Northern Germany habitually give cantharides to cows when 
backward in coming into heat at the proper season. 

According to Cautieri, toxic doses of cantharides rapidly lessen blood-pressure 
and the force of the cardiac pulsations, but markedly increase the pulse-rate. 

Cautieri found in animals killed with cantharides marked hyper- 
emia of the brain and spinal cord, and nephritis; Gallippe noted 
inflammation of the alimentary canal, kidneys, and bladder. 

The minimum fatal dose of cantharides is not certainly determined, 
and probably varies very much. According to Stille, twenty-four 
grains of the powder, taken in two doses, have caused fatal abortion, 
and an ounce of the tincture has destroyed life after the lapse of a 
fortnight. After death, intense injection, swelling, patches of exuda- 
tion, loss of epithelium, and other results of inflammation are found 
along the whole tract of the alimentary canal; intense hyperemia 
of the kidneys, with contraction and congestion of the bladder, also 
usually exists. According to the experiments of Aufrecht, all the 
forms of nephritis may be produced by cantharidin, but it is probable 
that in most cases of poisoning the first change is exudation of the 
white blood-corpuscles, rapidly followed by a desquamative nephritis, 
with profound alteration in the glomerules (see Ida Eliaschoff). 

There is no known antidote to cantharides, and the treatment 
of the poisoning must be conducted upon general principles. The 
stomach should be washed out repeatedly and freely by large draughts 
of warm water, aided by the stomach-pump or tube, or by a stimulat- 
ing emetic if the stomach-pump be not at hand. Large quantities 
of mucilaginous or albuminous drinks should be taken; and all oily 
substances should be avoided, as favoring the solution, and conse- 
quently the absorption, of the poison. Opium should be freely 



COUNTER-IRRITANTS 007 

exhibited, especially by the rectum, to allay pain and relieve the stran- 
gury. For the latter purpose warm sitz-baths or general baths should 
be employed. In some eases leeches to the epigastrium are advisable. 
When the suffering is very intense, the cautious use of anesthetics 
is not only justifiable, but imperative. 

Administration. — For blistering, the Cantharides Cerate is best 
spread upon sticking-plaster in such a way as to leave a margin about 
an inch in width, which shall adhere to the skin and hold the plaster 
in its place. In order for a blister to "draw" thoroughly, it usually 
has to be left on some eight hours; but in most cases the same result 
can be achieved with less suffering by allowing the blister to remain 
only five or six hours, or until decided redness and slight vesication 
have been induced, and then applying a flaxseed poultice. In cer- 
tain localities vesication requires a much longer application than that 
just spoken of; thus, upon the shaved scalp a blister will rarely act 
efficiently in less than twelve hours, and often not in that time. In 
maniacs, in the delirious sick, in children, and in other unruly patients 
it is often necessary to put on a blister in such a way that the sick 
person has no control over it. For this purpose the Cantharidal 
Collodion * may be used. It is ordinary collodion impregnated with 
cantharidin, and on evaporation leaves an adhesive blistering film: 
two or three coats of it should be applied by means of a camel's-hair 
brush. When there is any especial danger to be feared from absorption 
of the active principle, the use of the poultice, after a brief application 
of the blister as described above, should always be practised. 

RUBEFACIENTS. 
MUSTARD. 

The U. S. Pharmacopoeia recognizes two forms of mustard: White 
mustard (sinapis alba), the seeds of Sinapis alba, and as black mustard 
(sinapis nigra) the seeds of Brassica nigra. Both of these plants are 
European crucifers cultivated in the temperate regions of the world. 

Black Mustard yields on distillation a volatile oil, which does not 
pre-exist in the seeds, but is formed by the decomposition of sinigrin 
or potassium myronate in the presence of emulsin. The volatile oil of 
mustard is a colorless or yellowish fluid, of an intensely pungent, 
or corrosive, odor and taste. A momentary contact with it suffices 
to redden and blister the skin, and mucous membranes are said to 
be rapidly destroyed by its vapors. 

White Mustard contains sinalbin, which in the presence of water 
and emulsin forms acrinyl sulphocyanate, an oily, non-volatile, very 
acrid substance, upon which the activity of white mustard depends. 

Official Preparations : 

Charta Sinapis [Mustard leaves] External use. 

Oleum Sinapis Volatile External use. 

* For a case of poisoning by cantharidal collodion, see Phila. Med. Times, iv. 312. 



608 LOCAL REMEDIES 

Therapeutics. — .Mustard affords a most excellent material 
for the practice of mild revulsion. One advantage it possesses is the 
ease with which it can be controlled, all grades of action, from the 
mildest impression up to severe blistering, being at the will of the 
practitioner. It should be remembered, however, that the blister 
produced by it discharges but little, and is exceedingly sore and 
painful, as well as very slow and difficult of healing: so that, as an 
epispastic, mustard is in every way inferior to cantharides, and should 
not be employed. The black mustard is much stronger than the 
white, and must usually be diluted at least one-half (by the addition 
of flour or of flaxseed meal). The white variety may sometimes be 
employed pure, but generally it also should be reduced in strength. 

In many cases it is desirable to maintain for hours a mild, equable 
counter-irritant impression, and this may be done by adding from 
one to three teaspoonfuls of mustard, more or less, to a poultice of 
flaxseed. A mustard poultice (half-and-half black mustard, three 
parts to one of white mustard and flour) may generally be left on 
from twenty minutes to half an hour without danger of blistering. 
Weaker preparations may be used longer. 

A mustard plaster may be prepared like an ordinary poultice; but a very con- 
venient method is to take a newspaper folded to a little larger than the desired size, 
and tear open the front piece so that it can be folded back like a flap, leaving one 
edge attached; next, to spread upon the thick portion the mustard, leaving the 
edges free, and then to close the flap upon it and fold the edges back to the desired 
shape: when done with, this plaster can be thrown away, and no rags are lost. 
The mustard draws well through the single layer of newspaper covering it, and is, 
we think, less likely to leave troublesome after-soreness than when employed in the 
usual manner. 

A satisfactory counter-irritant application may also be made by saturating a 
piece of lint or canton flannel in a two to four per cent, alcoholic solution of the 
volatile oil of mustard, applying it in the same way as an ordinary mustard plaster. 

Capsicum and the stronger spices afford excellent materials for 
rubefaction. Cayenne pepper is nearly as strong as mustard, but is 
much less pleasant to handle, on account of the readiness with which 
it is diffused, and is much less frequently employed. Spice-plasters 
are useful when it is desired to make a steady, continuous mild 
impression, as in certain abdominal complaints. 

Spice-plasters may be made by the apothecary by means of the following recipe. 
Take of powdered ginger, gii; powdered cloves and cinnamon, each, gi; Cayenne 
pepper, jjii; tincture of ginger, f §ss; honey, q. s. ; mix the powders, add the tinc- 
ture, and sufficient honey to make of proper consistence for a stiff cataplasm. The 
domestic spice-plasters are much more elegant and cleanly than those made on the 
above plan. They are to be prepared as follows. Take equal parts of ground ginger, 
cloves, cinnamon, and allspice, and one-fourth part of Cayenne pepper, and thor- 
oughly mix them; then put the resulting dry powder into a previously prepared 
flannel bag of the desired size, distribute the powder equably through the latter, 
and quilt it in, — i.e., run lines of stitching across the bag, so as to confine the pow- 
der in little compartments: when using, moisten thoroughly with common whisky 
or with alcohol. A plan which has seemed to us still more pleasant is to put two 
ounces of unground ginger, an ounce of unground cloves, cinnamon, and chillies, 



COUNTER-IRRITANTS 609 

or African peppers, in a pint bottle, and pour whisky upon them. After this has 
.stood awhile, the liquor is to be pul upon a piece of flannel of the proper si/.e, and the 
latter is to be laid upon the pari anil covered with a. larger piece of oiled silk, or 
else a piece of spougiopilin may he employed. If the strength of the preparation 

is too great, it can readily be reduced by dilution; if it is too little, it can as readily 
l>e increased by adding more of the spices, especially of the peppers. In many 
eases, when the tenderness is very great, the weight of the spice-plaster is objected 
to. Under these circumstances the substitute here proposed is especially valuable. 

ARNICA. 

The Arnica montana is a perennial composite, native of Northern 
Europe and Asia, and said also to be found in the Northwestern 
United States. The yellow flowers which are the only portion of the 
plan! now recognized have about fourteen striated ligulate triden- 
fcate florets in the ray, twice as long as the disk, which consists of 
DUmerous tubular florets. Of its two alkaloids, arnicwe and cytisine* 
the latter is said to be identical with the active principle of the 
laburnum (Cytisus laburnum). 

Physiological Action. — Locally, arnica is stimulating, and, 
if in sufficient strength, decidedly irritating. Upon some skins the 
tincture acts even violently, rapidly developing an acute eczematous 
inflammation of the upper dermal layers, as manifested by hyperemia, 
papules, vesicles, excoriations, crusts, and scales in regular sequence. 

Neither the symptoms of poisoning by arnica nor its physiological 
action are well made out. 

According to H. A. Hare, arnica in dogs increases the activity of 
the cardio-inhibitory mechanism and also has a slight stimulant 
influence upon the heart. After large doses the pneumogastric nerves 
are paralyzed, the arterial pressure remaining near the normal. 
Stille has noted the same effects in man, namely, an increase of the 
cardiac action, and the respiration, elevation of the skin temperature 
and greater secretion of perspiration and urine. On the other hand, 
Balding asserts that the drug acts as an arterial depressant. 

The symptoms of poisoning seem strangely to vary between those 
of a violent gastro-intestinal irritant and those of a narcotic poison. 

Thus, in a woman, two cups of a strong infusion produced violent gastro-intes- 
tinal irritation, as shown by vomiting and choleraic diarrhoea, reduction of the 
pulse to 60, and finally collapse. In Barbier's case (quoted by Stille), an infusion 
of eighty grains of the flowers caused giddiness and intense muscular weakness, 
with spasmodic movements of the limbs. In another, not fatal, case, according to the 
statement of the patient, an ounce of the tincture did not produce any symptoms 
for eight hours, when approaching collapse, dilated, immovable pupils, with a cold, 
dry skin and a feeble fluttering pulse, rapidly supervened upon an intense epi- 
gastric pain, which was increased by pressure. In a not fatal case reported by W. A. 
Thorn, four hours after ingestion of a fluidounce of a tincture by a young man, the 
pulse was 100, full and strong, the temperature normal, insensibility complete, 

* J. L. Prevost and Paul Binet find that cylisine is a powerful centric emetic, which in large 
doses paralyzes the motor nerves. Its direct action upon the circulation is very slight; toxic 
doses cause a gradual lowering of arterial pressure and death by respiratory paralysis (Revue Mid. 
de la Suisse Rom., vii. and viii., 1887; see also R. Radziwillowicz, Thesis, Dorpat, 1887). 

39 



610 LOCAL REMEDIES 

conjunctiva anesthetic, respirations 18 per minute, no vomiting or purging. Twelve 
hours later the patient became wildly delirious; the next day he suffered from 
burning pain in the abdomen, diarrhoea, and free diuresis. 

Therapeutics. — In the present state of our knowledge, the 
internal use of arnica is experimental. Externally.it is employed as 
a stimulant application in bruises and sprains, generally in the form 
of tincture (Tinctura Arnica — twenty per cent.), which may be 
applied pure. Sometimes fomentations of the flowers are employed. 
Its property of occasionally producing intense dermal irritation should 
be borne in mind. 

Burgundy Pitch was formerly official. It is a concrete juice 
obtained by wounding the Abies excelsa, or Norway spruce, — lofty 
forest trees of Middle and Northern Europe, — melting the product 
of the exudation with hot water, and straining. It is hard, opaque, 
brittle, of a feeble terebinthinate odor and taste, and contains resin 
and a minute amount of volatile oil. It is a mild rubefacient, which, 
in the form of plaster, may be kept applied for a long time in chronic 
bronchitis and in rheumatic affections of the trunkal muscles. The 
plaster contains fifteen per cent, of wax. The Warming Plaster 
contains one part of cantharides cerate to twelve parts of Burgundy 
pitch, and is a very decided counter-irritant whose prolonged use 
will sometimes blister. 

Carbon Distjlphide. — Carbon Bisulphide is a clear, colorless, 
highly refractive, very volatile liquid, of a strong, disagreeable odor 
and a sharp aromatic taste. It is very much used in the arts as a 
solvent, and is an active poison, half an ounce of it having produced 
death, preceded by coma, with collapse and abolition of reflexes. 
It has not been used as an internal remedy, but has been emploj'ed 
as a counter-irritant and local anesthetic for the relief of focal, facial, 
and other neuralgias. A small dossil of cotton, saturated with the 
drug, should be placed on the part and covered with wax paper; or 
better, a wide-mouthed bottle containing the disulphide and cotton 
may be inverted upon the part for a few minutes. Even the 
counter-irritant use of carbon disulphide is not to be encouraged. 






REFERENCES. 

COUNTER=IRRITANTS. Huseman.v Handb. der Toxicologic 

..C.M.W., 1882 xx. 850. Pall - journ.^de Pharm. et de 

sk d£v 237 Chim. June, 1871. 

V A P. A xciv 323. Thompson Brit. Med. Jour., 1887. 

G H M (5' 1874 439 Thornton Virginia Med. Monthly, 

B. M. S. J., Jan. 12, 1888. Sept., 1883. 



Balding. . 

Cautieri 

Eliaschoff. . . . 

Galippe 

Hare 



FAMILY X.— ESCHAROTICS. 



ESCHAROTICS arc drugs which are used to destroy diseased or 
sound tissue. Many of them exert a purely chemical influence, while 
others seem to destroy life by directly affecting the vitality of the 
part, and are said to act dynamically. Those which act chemically 
do so in several ways: some, like bromine, probably produce an 
intense corrosive oxidation, while others, like sulphuric acid, abstract 
the water. 

Escharotics are used for various purposes. Formerly they were 
employed to open abscesses; but in the very few cases in which the 
knife is not allowable, aspiration usually affords a superior and safer 
method. They are constantly applied to destroy unsound, harmful 
tissues and growths. Thus, they are used to remove the specific 
tissue of a chancre, or to kill a malignant or semi-malignant tumor. 
Another purpose which they fulfil is the destruction of poisoned 
wounds. In these cases they may in some instances destroy the poison 
itself, but at other times they simply prevent the absorption of the 
toxic agent by putting an end to the life-actions of the tissue contain- 
ing it. It is hardly necessary to mention all the various cases in which 
caustics are employed to overcome the effects of poisoned wounds. 
Hydrophobia is a perfectly uncontrollable disease; but the thorough 
destruction of the wounded tissue at any time before the manifesta- 
tion of the symptoms will probably prevent its occurrence, as it 
certainly will if performed early. In malignant pustule, life depends 
upon the free early use of escharotics. Escharotics are employed 
to produce ulcerations which shall be the bases of issues; also, by 
destroying the exuberant granulations or the indolent surfaces of 
ulcers, to remove at the same time diseased tissue, afford protection 
to the parts below by forming an impermeable surface, and exert 
such alterative action upon the part as shall modify for good the 
life-processes. 

It is evident that the choice of the caustic should depend upon the 
object to be attained. When large tumors are to be killed, or when it 
is all-important completely to destroy a poisoned wound, a powerful 
deep-reaching escharotic must be employed; but when the surface 
of an ulcer is to be filmed over, a caustic which acts superficially 
and forms a dense albuminous coating, as does silver nitrate, is 
to be chosen. 

An observation of N. A. Randolph and S. G. Dixon indicates that 
the pain produced by a caustic may be almost nullified by the use of 
cocaine. They find that the saturated solution of cocaine in nitric 

611 



612 LOCAL REMEDIES 

acid acts as powerfully as nitric acid, although much more slowly, 
and that the only sensation experienced during the production of 
even a deep eschar is a slight prickling. 

All of the more powerful of the escharotics, when taken inter- 
nally in sufficient amount, act as violent corrosive poisons, producing 
agonizing pain in the oesophagus and hypogastrium, violent bloody 
vomiting, often purging of similar character, and finally collapse, 
deepening into death, which is sometimes preceded by convulsions. 
When the dose is not so large, the patient may rally from the imme- 
diate effects of the poison, to succumb finally to the local lesions 
produced, or to struggle through a protracted convalescence to 
health, perhaps only to die years afterwards from organic stricture, 
caused by the ulcerations of the oesophagus or other digestive tubes. 
The first indication in poisoning by one of these substances is to 
neutralize or chemically antidote the poison: with the alkalies, 
dilute acid, generally convenient in the form of vinegar; with the 
acids, alkalies, usually at hand in the shape of whitewash or of soap; 
with other poisons, specific antidotes. Opium should always be 
freely given, and the symptoms during and after the first poisoning 
be treated as they arise. 

Potassium Hydroxide. — When potassium hydroxide is placed 
upon the skin it soon melts, and, as it does so, gives rise to a pain 
which increases until it becomes very intense, and continues until 
the power of the alkali is so diminished that it can no longer reach 
through the tissue it has killed to the sound flesh below. Under 
the action of the escharotic the skin becomes of a dirty ashen-gray, 
and finally a slough is formed, with inflammation of the surrounding 
parts, and ulceration and detachment of the dead tissue in from six 
to ten days. The potash appears to act chiefly by abstracting the 
water, and, to some extent, by combining with the fatty and other 
portions of the tissues. Its slough being perfectly permeable, and its 
power being but slowly expended by its own action, potassium 
hydroxide is one of the most thorough of the escharotics: it is, there- 
fore, to be preferred when a very deep and decided influence is 
required, as after the bite of a rabid dog. It is somewhat uncontrollable 
in its action, and requires care in its use. The best method of appli- 
cation is as follows. Take a piece cf thick adhesive plaster, and cut 
a hole in it of such size that, when the piece is warmed and properly 
placed upon the skin, the part to be acted upon will be exposed while 
all around it will be protected. Then apply the plaster, and grease 
the outer surface of it, without allowing any of the oil to come in 
contact with the exposed central skin. Then lay the caustic potash 
upon the latter, and, when the action is believed to have extended 
deep enough, wash the part with dilute vinegar. 

Vienna Paste, a grayish-white powder, composed of equal 
amounts of potassium hydroxide and caustic — i.e., unslacked — lirne. 



ESCHAROTICS 613 

li is not SO active as caustic potash, but is loss likely to spread ami 
diffuse itself. It is to be mixed with sufficient alcohol to form a 
paste, and then applied like caustic potash. 

Piedagnel affirms that this caustic may he rendered nearly or entirely painless 
by mixing one pail of morphine hydrochloride with three parts of the powder, and 

i hen by the addition of chloroform forming a paste that may be spread upon lead 
plaster and so applied. In five minutes the skin under the application becomes of 
a dead-white color, and at the end of fifteen minutes is brown and carbonized. If 
the application be persisted in, the thickness of the eschar will become finally about. 
equal to that of the layer of the paste employed. Cocaine would probably be more 
efficient in preventing pain than the morphine. 

Arsenic Tkioxide. — As a caustic, arsenic is energetic and 
powerful, but somewhat slow, and causes intense pain, with violent 
inflammation of the neighboring parts. It is stated to affect more 
rapidly morbid than normal structures, and is especially used for the 
destruction of malignant growths. It appears to act chiefly upon 
the vitality of the part, acting, when sufficiently diluted, as a powerful 
irritant, and when in a concentrated form producing an irritation so 
intense that life cannot endure it. Hence, probably, the reason of 
its affecting more rapidly morbid growths, which have a lower vitality 
than sound tissues. 

The great objection to the employment of arsenic is the possibility 
of its absorption in sufficient amount to cause constitutional symp- 
toms: even death has resulted from its external use. Since absorp- 
tion takes place much more rapidly in a healthy than in an intensely 
inflamed or a dead tissue, whenever arsenic is employed as a caustic 
it should be used so freely as to kill the tissues rapidly, and under no 
circumstances should it be applied to a fresh wound. Used in any 
way, arsenic is a hazardous caustic, and it ought to be employed 
only with the knowledge and distinct remembrance of this fact. 
Cancer, and perhaps some forms of semi-malignant ulceration, such 
as lupus, appear to be the only diseases which justify its use. 

There is no reason for believing that any of the almost innumerable 
substances which have been proposed as a basis for arsenous pastes 
possess peculiar advantages: the only needful direction is to mix the 
caustic with from eight to ten times its bulk of inert material of such 
a nature as to make either an ointment or a paste, and to allow this 
to remain on the part for from eighteen to twenty-four hours. 

Zinc Chloride. — Zinc Chloride occurs in broken fragments of 
a grayish-white color, or as a white or nearly white granular powder, 
translucent and waxy in appearance, of an acrid corrosive, or, when 
diluted, acrid astringent, metallic taste. It is extremely deliquescent, 
fusible, volatilizable at a high temperature, and very soluble in both 
water and alcohol. Zinc chloride is a very powerful caustic, pro- 
ducing, when applied in a concentrated form, intense pain lasting 
from six to eight hours, and a whitish eschar, which usually separates 
in from six to twelve days. Its penetrating powers are a little less, 



614 LOCAL REMEDIES 

and its action more readily controlled, than is that of potash; its 
absorption does not endanger life, as is the case with arsenic trioxide; 
and it leaves a slough which is free from odor. 

Canquoin's Paste is made by mixing zinc chloride with flour and 
water. The strength varies according to the purpose, the weakest paste 
containing only one part of the caustic in six parts; the strongest, one 
part in three. When used, ten or fifteen drops of water are added to 
the paste, which is applied in layers, successive applications being 
required when a large tumor is to be destroyed. Anhydrous calcium 
sulphate has been especially commended by A. Ure, as forming a 
drier paste with the escharotic and limiting its action more definitely 
to the site of application than any other substance. Concentrated 
alcoholic or aqueous solutions of zinc chloride are often used as 
caustics in cases of chancres and other small specific ulcers, and are 
reputed to be efficient. They should be applied by means of little 
pledgets of lint. As the action of the chloride upon the skin is slow 
and very painful, whenever the cuticle over the part to be destroyed 
is sound it should be removed by means of blisters. By some sur- 
geons the escharotic is introduced directly into the tumor to be 
destroyed. The official solution (Liquor Zinci Chloridi) has been 
used as a disinfectant, but is of very little value. 

Mercury Bichloride. — Corrosive Sublimate is an escharotic of 
moderate power, which shares the dangers of arsenic, since death 
has followed its external use. In saturated solution it is much used 
as a caustic in chancres, but is scarcely equal to the solution of mer- 
curic nitrate. In these cases it should be applied by means of a 
camel's-hair brush. The late George B. Wood recommended very 
highly that in onychia maligna a powder composed of equal parts of 
corrosive sublimate and zinc sulphate intimately mixed should be 
sprinkled thickly over the diseased surface, and a pledget of lint 
thoroughly wet with laudanum laid thereon. There is severe pain 
for half an hour to an hour; but the dressings are not to be removed 
until eight or ten hours have elapsed. When the slough which is 
thus formed separates, a healthy granulating surface is left. 

Mercuric Nitrate. — The solution of Mercuric Nitrate {Liquor 
Hydrargyri Nitratis) is a nearly colorless, highly corrosive, acid 
liquid, having a specific gravity of 2.086, and made by dissolving 
mercury, or its red oxide, in a large excess of nitric acid. Its appli- 
cation to a space not bigger than a half-dollar has produced very 
serious poisoning.* It is rarely used, except for the purpose of de- 
stroying specific or cancerous ulcers. It is especially useful in chancres, 
to which it should be applied with a glass rod. In obstinate acne, 
an indolent tubercle may be destroyed b} r a minute drop without 
producing a scar. It has been largely employed by gynecologists 

* Case, Lancet, January 3, 1874. 



ESCHAROTICS G15 

in ulcerations of the cervix uteri. Its action is very prompt and is 
moderately deep; the pain is severe, but transient. 

Nitric Acid is a powerful caustic, which is never employed to 
destroy large tumors, but is a favorite application to chancres, to 
syphilitic, phagedenic, and other unhealthy ulcers, and to condylomata 
and other small dermal growths. A drop or two may be applied by 
means of a glass rod or a wood splinter, and when the action has 
gone far enough, neutralized with sodium carbonate or soapsuds. 

Chromium Trioxidk. — Chromii Trioxidum, commonly known 
as Chromic Acid, occurs in anhydrous acicular crystals, of a deep 
purplish-red color, and an acid, metallic, corrosive taste. They are 
very deliquescent, melting down, when exposed to the air, into an 
orange-red solution. Chromium trioxide is a very active oxidizer, 
and when mixed with organic matter rapidly alters it, and if in slight 
excess will dissolve almost any form of tissue. It is used to destroy 
condylomata and other dermal growths, and is best applied by means 
of a glass rod, the liquid formed by the spontaneous deliquescence 
of the crystals being used. Chromic acid is sometimes prescribed, 
dissolved in or made into a paste with glycerin, but it is stated that 
in mixing the two great care must be taken to add the liquid slowly, 
drop by drop, as otherwise there is danger of an explosion. In the 
German army, painting the soles of the feet and the skin between the 
toes with a nve-per-cent. solution of chromic acid is said to have 
had a very great influence in increasing the marching powers of the 
troops, by arresting excessive sweating, and hardening the skin. 
Chromic acid is a violent corrosive poison, a single drop of the satu- 
rated solution having caused very severe symptoms.* The nature of 
the poison may often be recognized by the reddish-brown, or more 
rarely greenish, discoloration of the skin of the lips and of the mucous 
membrane of the mouth and gullet, but this discoloration may be 
absent. In a number of cases death has resulted from the too free 
external use of the acid.f 

Trichloracetic Acid. — Acidum Tricolor aceticum occurs in del- 
iquescent crystals. It has been used to a considerable extent for the 
destruction of papilloma and other growths; a single crystal placed 
on a growth produces immediately a white, dry, adherent mass, 
which falls off in a few days. The pain is said to be not at all severe, 
and may be entirely prevented by the use of cocaine. 

Bromine is a dark brownish-red liquid which has a very power- 
ful, disagreeable, chlorine-like odor, and at ordinary temperatures 
emits exceedingly acrid, pungent fumes. It is sparingly soluble in 
water, more soluble in alcohol, and still more so in ether. When 

* Case, Brit. Med. Journ., 1889, i. 

t For experimentsas to its effects on animals, see A.E. P.P., vi.; also Strieker's Jahrb., 1877, 139. 
For cases of poisoning, see S.J., 1884, cci. 129; U.M.M., ii.; M.M.W., 1903, i. 691; D. A.K.M., lxxv. 



..it; LOCAL REMEDIES 

brought into contact with organic matter, it oxidizes and completely 
destroys it with great rapidity. On account of this property and of 
its liquid form, bromine is one of the most severe, thorough, and 
rapid of all the caustics. It has not been much employed to destroy 
morbid growths, but has been found very efficient in hospital gangrene. 
After most of the slough has been cut away, the caustic should be 
applied pretty freely to the living tissue by means of a glass rod. When 
taken internally, bromine acts as a very powerful corrosive poison.* 
Zinc Sulphate, Copper Sulphate, and Burnt Alum are feeble escha- 
rotics, used only to destroy exuberant granulations in ulcers. 

Pyrogallol. — Pyrogallic Acid is a triatomic phenol which may 
be prepared synthetically, but is usually obtained, in accordance with 
the directions in the U. S. Pharmacopoeia, as the result of the igneous 
decomposition of gallic acid. In concentrated form it is a powerful 
caustic, and as such, and also in the form of dilute ointment or solu- 
tion, five to forty grains to the ounce, has been considerably used in 
the treatment of lupxis, psoriasis, and allied affections of the skin. 
It is a violent poison, and in various cases death has followed its too 
free external use. Half an ounce of it, taken internally, has produced 
death in four days. The symptoms which follow its external use 
have been malaise, vomiting, diarrhoea, headache, pallid and cyanosed 
lips, collapse, a peculiar greenish hue of the skin, rapid pulse and 
respiration, albuminous urine, becoming dark brown or black from 
the presence of methemoglobin, icterus, insomnia, restlessness with 
diminished reflexes, and death preceded by delirium, convulsions, 
and coma. In pregnant women abortion without death of the mother 
has occurred as the result of the external use of the ten-per-cent. 
ointment of the pyrogallol, in psoriasis (Busch). When the poison 
has been due to the internal use, violent burning pains, black vomit, 
and other evidences of its irritation to the gastro-intestinal tract are 
usually present. As noted by Personne, these symptoms resemble 
those of phosphorus-poisoning, and wide-spread fatty degeneration 
and other post-mortem lesions similar to those caused by phosphorus 
are found after death. 

Lactic Acid. — Under the title of Acidum Lacticum the U. S. 
Pharmacopoeia recognizes a preparation containing seventy-five per 
cent, of absolute lactic acid. The suggested use of this remedy, as 
a hypnotic, has passed into a deserved desuetude. The only prac- 
tical use to-day of lactic acid, is as a caustic in laryngeal and dermal 
tuberculosis and similar ulcerative conditions. 



REFERENCES. 



Bosch W. K. W., 1901. Personnr C R. A. S., 1869. 

Piedagnki Journ. de Pharm. et de Randolph and Dixon.. M. News, Jan. A, 

C:rim., 3 s., xxxiii. 188.5. 

* For cases, see Schmidt's Jahrb., ccxxi.; also Yierteljahr. j. Gerichtl. Med., 1889. 



FAMILY XI. DEMULCENTS. 



These are bland substances, which form more or less gummy or 
mucilaginous solutions in water, capable of exerting a calming or 
soothing influence upon inflamed surfaces. Their action is probably 
purely mechanical, their adhesiveness causing the water they are in 
to remain long upon the part; they are, as it were, vehicles for water, 
the demulcent par excellence. It has been affirmed not only that 
demulcents soothe surfaces to which they are immediately applied, 
but also that taken internally they relieve irritation in distant organs. 
There is, however, no reason for supposing that such of them as 
escape digestion are absorbed or yield to absorption any principles 
in sufficient quantity to exert an influence upon the general system. 
The relief which undoubtedly follows their use in certain affections 
of parts which they can reach only through the circulation is prob- 
ably due to the large quantities of water with which they are admin- 
istered, lessening the concentration, and hence the acridity, of the 
urine and other secretions. 

Clinically, demulcents are useful as local applications in all forms 
of acutely inflamed surfaces, and they are taken internally in acute 
inflammatory conditions of the alimentary canal. In slight bronchial 
irritation they are often of service, especially when allowed to dis- 
solve slowly in the mouth: used in this manner, they not only exert 
an influence upon the mucous membrane of the mouth, but very 
probably find their way also into the respiratory passages. 

ACACIA. 

Gum Arabic is a gummy exudation from Acacia Senegal, and 
other species of Acacia, small trees growing in Northern Africa, 
Senegambia, Guinea, etc., the Cape Colony, and Australia. Gum 
arabic occurs in roundish or irregular pieces, more or less transparent, 
hard, brittle, varying in color from white or yellowish white to red, 
or even deep orange brown. It consists of a peculiar, feebly acid, 
amorphous principle, Arabin, united with about three per cent, of 
lime, potassium, and magnesium oxide. In the plant, arabin, like 
other gums, appears to be formed by a retrograde metamorphosis 
of cellulose. On account of its solubility in water and pleasant taste, 
gum arabic is often used as a demulcent in irritation of the fauces 
and in angina. It is sometimes employed as an addition to drinking- 
water in fevers, and is believed to have slightly nutritious 
properties. Its chief use, however, is in Pharmacy, in the making 
of emulsions, pills, etc. 

617 



618 LOCAL REMEDIES 

Official Preparations : 

.Mucilago Acaciae Vehicle. 

Syrupus Acaciae Vehicle. 

Tragacanth (Tragacantha) is the concrete juice of Astragalus 
gummifer, an<l of other species of Astragalus, a small shrub of Asia 
Minor. Tragacanth occurs in large, whitish, horny, waved flakes, or 
sometimes in filamentous pieces. It is odorless and nearly tasteless. 
Introduced into water it does not dissolve, but swells up into a soft 
paste. One hundred parts of it contain, according to Guerin, 53.3 
parts of arabin, 33.1 parts of bassorin, and 2.5 parts of inorganic 
ash. Bassorin is a gummy principle, at once distinguished from arabin 
by its not dissolving in water, but simply swelling up into a pasty 
mass. Tragacanth is used only in the manufacture of troches and in 
suspending heavy powders, for which purpose the difficulty of its 
solution and the extreme viscidity of its mucilage especially fit it. 
Its mucilage (Mucilago Tragacanth^) is used in varying dose 
as a vehicle. 

Ulmus. — Slippery Elm is the inner bark of Ulmus fulva, a 
large indigenous tree. The bark is of a yellowish-white or tan color, 
fibrous, yet when dry somewhat brittle, and occurs in long, flat strips 
or pieces one or two lines thick. It is pleasantly mucilaginous when 
chewed. It contains a large quantity of a peculiar mucilage, which 
it yields freely to water. Its infusion is sometimes taken in large 
quantities in inflammations of the intestines, as a demulcent laxative; 
but its chief use is as an external application. When ground into 
powder, slippery elm makes an excellent soothing poultice. The 
mucilage (Mucilago Ulmi) is used in varying dose as a vehicle. 

Chondrus. — Irish Moss, or Carrageen. — The fronds of Chondrus 
crispus, a sea-weed growing on the coast of Ireland, and 
also on the northern coast of the Lmited States, where it is now 
gathered in large quantities. The fronds are purplish red, — but, as 
kept in the shops, bleached by washing in fresh water, whitish and 
translucent, — cartilaginous, slender, much branched, swelling up 
but not dissolving in water, and having a slightly saline taste. Their 
virtue depends chiefly upon a starch- or gum-like principle, Carra- 
geenin, which is distinguished from starch by not turning blue with 
iodine, and from gum by not precipitating from its watery solution 
on the addition of alcohol. Chondrus also contains a notable 
proportion of a vegetable albumen. 

Carrageen, being demulcent and nutritious, is employed as an 
article of diet in those cases requiring food of such character, and 
may be used instead of arrow-root. It is to be prepared by first 
soaking for ten minutes in cold water, and then boiling from half an 
ounce to an ounce of it (according to the desired consistency) in a 
pint and a half of water down to a pint, sweetening and flavoring to 
taste. Milk may be substituted for water. 



DEMULCENTS til!) 

Glycyrrhiza. — Licorice Root is the root of Glycyrrhiza glabra 
and glandulifera, native herbs of Southern Europe. It occurs in 
long, cylindrical pieces, from a few linos to more than an inch in diam- 
eter, brownish externally and yellowish within. Its fracture is fibrous, 
its taste sweet and mucilaginous, its odor none. Its active principle 
is Glycyrrhizin. This is a sweet, neutral substance, differing from the 
sugars in not being converted by nitric acid into oxalic acid, and by 
its inability to undergo the vinous fermentation. 

Official Preparations : 

Extractum Glycyrrhiza [Licorice] Vehicle. 

Kxtraetuin (ilyeyrrhizic l'urum Vehicle. 

Glycyrrhizinum Ammoniatum 5 to 10 grains (0.3-0.6 Gm.). 

l'luidext lactam Glycyrrhizffi Vehicle. 

Elixir Adjuvans Vehicle. 

Mistura Glycyrrhizse Compoaita [Brown Mix- 
ture] (Licorice 3, Camphorated Tincture of 
Opium 12, Wine of Antimony 6, Spirit of 
Nitrous Ether 3 per cent.) i to 1 fluidounce (15-30 C.c). 

Trochisei Glycyrrhiza? et Opii (Each contains 
^5 grain (0.005 Gm.) Opium) 

Licorice root is very largely used as a demulcent in pectoral 
complaints, and, on account of its pleasant taste, as a means of 
disguising or of flavoring medicines. In the form of glycyrrhizin it is 
said to conceal almost entirely the bitter taste of quinine and similar 
substances. It is used almost exclusively in the form of the extract, 
known as Licorice. The compound mixture of glycyrrhiza is much 
used as a domestic remedy in colds and the early stages of mild bron- 
chitis. The ammoniated glycyrrhizin is an elegant demulcent prepa- 
ration which, however, is incompatible with acid or alkaline solutions. 

Linseed or Flax-seed is the seed of Linum usitatissimum, or 
common flax, and contains large quantities of mucilage and of oil; 
its infusion, Flax-seed tea, is much used internally. It is often made 
with boiling water; but the application of too much heat causes the 
extraction of the oil, and renders the preparation less palatable. The 
addition of lemon and sugar makes it more palatable. It may be 
drunk ad libitum in pectoral catarrhs, in enteritis and dysentery, and 
in irritation of the kidneys or the urinary passages. 

Starch. — Obtained from Indian corn, a white, inodorous, taste- 
less powder, composed of microscopic granules, is physiologically 
inert except as a food. It is often used as a dusting powder in irri- 
tant conditions of the skin; as a soothing demulcent in the prepara- 
tion of opiates and other rectal injections, and pharmaceutical^ 
for the purpose of thickening or gelatinizing ointments, and the 
making of paste for use in skin diseases. 

Medulla Sassafras, or Sassafras Pith, yields a delicate mucilage 
much used in eye diseases (Mucilago Sassafras Medulla, U. S.). 



620 LOCAL REMEDIES 

Alth.ea. — The roots of Althaea officinalis yield a bland muci- 
lage; their decoction is sometimes given in gastric irritation, and 
their syrup (Syrupus Althjeje, U. S. 1890) is used as a vehicle. 

Cetraria.- — Icelanc M -s is the fronds of a lichen, Cetraria islandica, growing 
on rocks in Iceland and i. ::. >st of the northern portions of the world. It is said 
to be abundant in the moui.'jains of New England. The foliaceous, dry, shining, 
lobed, and laciniated fronds are about four inches long, of various intermixed colors, 
gray, brown, and red, and of a mucilaginous, bitter taste. Iceland moss contains 
a peculiar lichen starch and a bitter principle. It yields to cold water its bitter- 
ness; to boiling water all of its virtues. Cetrarin, or Cetraric Acid, is the bitter 
principle, which may be obtained as a snow-white mass of interlaced acicular crystals. 
It unites with alkalies to form salts. With it in the lichen is associated in small 
quantities lichenstearic acid. Kobert has found that cetrarin lias no effect upon 
the arterial pressure; also that in toxic dose it produces violent convulsions in the 
cat and in the dog, while in small dose it distinctly increases the activity of the 
motor area of the brain and spinal cord. Kobert also asserts that in healthy men 
cetrarin increases the number of the red and, in a still greater degree, of the white 
corpuscles; and believes that in chlorosis and anemia, especially when there is 
constipation, cetrarin will prove a valuable remedy. 

Lichenin, or Lichen Starch, the mucilaginious, nutritive principle of Iceland 
moss, differs from ordinary starch in not being deposited in granules within the cells, 
but in layers or irregular masses between the cells, or indeed forming the walls 
of the cells (De Bary). In cold water it swells up without dissolving; in hot water 
it dissolves, and on cooling condenses into a jelly. With iodine it strikes a yellow, 
green, or sometimes rather faint blue, color. It is found in very many lichens; also 
in many species of sea-weed, notably in the so-called Corsican moss. 

Iceland moss has enjoyed some reputation as a demulcent in pectoral com- 
plaints. From its bitter principle, it is somewhat tonic, and its lichenin is probably 
about equal to ordinary starch as a nutrient. When prepared as an article of diet, 
in the form of jelly, the bitter taste should be removed by soaking for some hours 
in a very weak, cold alkaline solution, and afterwards for a little while in cold water. 

Hordeum. — The decorticated seeds of the common barley constitute the pearl 
barley of commerce. They contain starch and mucilage, and the decoction was 
formerly official. Barley water is used as a nutritious, demulcent drink in fevers 
and inflammatory conditions, especially when the gastric mucous membrane is 
involved. The U. S. Pharmacopoeia of 1870 directed that it should be prepared as 
follows: "Take of barley two troy ounces; water a sufficient quantity. Having 
washed away the extraneous matters which adhere to the barley, boil it with half a 
pint of water for a short time and throw away the resulting liquid. Then, having 
poured on it four pints of boiling water, boil down to two pints, and strain. " 



REFERENCES. 



De Bary Hofmeister's Handbuoli d. Kobert Verhand. d. Internat. Bed, 

Physiol. Botan., ii. 25.5. Cong. Berlin, 1S90. 



FAMILY XII.— OIOLLIENTS. 



Tun: emollients are perfectly bland, fatty substances, which, 
when applied to the skin, soften it and render it more pliable. The 
action of these remedies is largely mechanical, and they probably 
soften the derm in precisely the same way as they affect a raw hide or 
a piece of leather. They are therefore especially useful when the skin 
has a tendency to crack or to chap. Whenever surfaces become 
sore by attrition, or, in other words, chafe, emollients are al;o useful 
mechanically. They often afford relief in simple inflammations of 
the skin under such circumstances that their action cannot be 
explained as purely mechanical: indeed, they seem to exert a dynamic 
influence upon the nutrition of the parts concerned. It may be that 
they shut out or interfere with the development of pathogenetic 
germs, or, in other words, that they are mechanical antiseptics. Be 
these things as they may, clinical experience has demonstrated that 
fatty matters are of very great value in the treatment of superficial 
inflammations. 

The blandest fat, when it becomes rancid, is very irritating, and 
will do more harm than good, so that the strictest attention must 
be paid to the condition of the fatty material employed. Any per- 
fectly bland oily substance may be used as an emollient. 

The fatty bases are also used largely as a means of introducing 
drugs into the general system. This, the so-called endemic method 
of administering remedies, is used especially for drugs which are likely 
to irritate the gastro-intestinal tract. The disadvantages of this 
channel of absorption are its slowness and the uncertainty of dosage. 
There does not appear to be any marked difference in the power of 
true fats in penetrating the skin, excepting in so far that a hard fat 
does not readily melt at the temperature of the body, and therefore 
does not yield itself to absorption so readily as does a soft one. The 
petrolatums, however, are not at all fitted for ointment bases when 
systemic effects are desired. 

The fats are combinations of either oleic, palmitic, stearic acid or 
allied substances with glycerol. Most fats contain more than one of 
the fatty acids. The consistence depends upon the relative propor- 
tions of the various fatty acids. The most fluid of the ordinary fats 
is olein, and the most solid is palmitin, stearin occupying a position 
midway between them. 

There are certain substances, as petrolatum and glycerol, which 
while not fats, in the proper sense of the word, have similar 
emollient virtues and are therefore considered in this family. 

621 



(i: 



LOCAL REMEDIES 



Official Fats and Ointment Bases : 

Congealing or 
Official Name. Common Name. Consistency. Melting Point. 

Acidum Oleicum Oleic Acid Liquid 39.2° F. 

Aeidum Stearicum Stearic Acid Solid 133°-15o° F. 

Adeps Lard Soft 100.4°-104° F. 

Adeps Benzoinatus Benzoinated Lard Soft 

Adeps Lanaa Wool-fat Soft 104° F. 

Adeps Lanae Hydrosus Lanolin Soft 104° F. 

Cetaceum Spermaceti Solid 113°-122° F. 

Sevum Praeparatum Mutton-suet Solid 113°-122° F. 

Cera Alba White Bees-wax Solid 147°-149° F. 

Cera Flava Yellow Bees-wax Solid 144°-147° F. 

Oleum Adipis Lard Oil Liquid 32° F. 

Oleum Amygdalae Expressum Oil of Sweet Almond Liquid -4° F. 

Oleum Gossypii Seminis Cotton Seed Oil Liquid 23°-32° F. 

Oleum Lini ' Linseed Oil Liquid -4° F. 

Oleum Olivae Olive Oil Liquid 32° F. 

Oleum Ricini Castor Oil Liquid 0° F. 

Oleum Theobromatis Cocoa-butter Solid 86°-05° F. 

Glycerinum Glycerin, Glycerol Liquid 

Paraffinum Paraffin Solid 125°-135 G F. 

Petrolatum Vaseline Soft 113°-118° F. 

Petrolatum Album White Vaseline Soft 113°-118° F. 

Petrolatum Liquidum Albolene Liquid 

Official Mixed Ointment Bases : 

Ceratum White Wax 30, White Petrolatum 20, Benzoinated 

Lard 50 per cent. 

Unguentum White Wax 20, Benzoinated Lard 80 per cent. 

Unguentum Aquae Rosse .... Spermaceti 12.5, White Wax 12, Expressed Oil of 

Almond 56, Sodium Borate 0.5, Stronger Rose 

Water 19 per cent. 
Glyceritum Amyli Starch 10, Water 10, Glycerin 80 per cent. 

Olive Oil is the ordinary salad oil of the table, and may be used 
wherever a very bland oil is desired. It has, however, no superiority 
for ordinary purposes over the Cotton-seed Oil, indeed, a very large 
proportion of the olive oil of commerce is cotton-seed oil; it is credibly 
affirmed that more cotton-seed oil is exported from New Orleans to 
the Mediterranean cities than olive oil is exported from those ports, 
much of the cotton-seed oil coming back with olive oil labels. There 
seems to be no sufficient reason for believing that olive oil differs 
from cotton-seed oil in its physiological or therapeutic properties. 
These oils are sometimes used internally with advantage, for nutri- 
tive purposes, and are also very mildly laxative. The assertion, 
originally made by Kennedy, that large doses of olive oil are very 
useful against biliary calculi, has received strong clinical confirmation. 
S. Rosenberg found that in dogs with biliary fistulse olive oil not only 
increased the amount of bile, but also rendered the bile much more 
liquid. Since fats are absorbed chiefly, if not entirely, through the 
thoracic duct, it would appear that the oil must pass through the 
pulmonary circulation before reaching the liver. This is confirmed 
by the experiments of Chauffard, who could not find in the bile- 



EMOLLIENTS 623 

duct or gall-bladder any trace of oil which he had injected into the 
stomach of the dog. If olive oil lias the asserted remedial influence, 
it probably acts reflexly through the nervous system, — through a 
mechanism provided by nature for the purpose of aiding in the diges- 
tion of fats when in excess. The dose of the oil should be not less than 
from five to seven fluidounces (150-215 C.c.) taken in four to eight 
portions in not longer than three hours. It may be given in 
aromatized emulsion, with a little brandy or whisky if desired. 

Oil of Theobroma on account of its firm consistency and com- 
paratively low melting point is largely used for making suppositories 
and bougies. 

Wool-Fat is obtained from the wool of sheep, which is said to 
contain, on an average, forty-five per cent, of it. It appears to be 
practically the same as the natural oil of the hair in man and other 
animals.* The Hydrous Wool-Fat contains about thirty per cent, 
of water, and is the form of the unguent ordinarily employed. It 
was first recommended by Oscar Liebreich as a basis for ointments 
or preparations to be applied to the surface of the skin. It is entirely 
free from irritant properties, has the power of taking up a large amount 
of water without losing its unctuousness and does not easily become 
rancid; it has been asserted that it is absorbed through the skin 
much more readily than are other fats. In the experiments of Patsch- 
kowsky, half an hour after inunction with lanolin and potassium 
iodide the iodine was recognized from the urine, while official potas- 
sium iodide ointment yielded negative results. This has been con- 
firmed by Kaspar, but Ritter and Pfeiffer obtained contrary results, 
and in a considerable series of experiments were unable to perceive 
that lanolin had any superiority over other fats in promoting 
absorption. The facts, moreover, that lanolin is largely the secretion 
of sebaceous follicles, contains an abundance of cholesterin, and is 
in the nature of a waste product which is intended, not for absorption 
but for the keeping soft of the skin and its appendages, indicate very 
strongly that it will yield itself, and medicinal substances with which 
it may be impregnated, less readily to absorption than do other fats. 
As a basis of ointments used to medicate the skin it is most effective, 
but when absorption is desired it is probably inferior as a vehicle 
to ordinary fats. 

Petrolatum. — The solid basis of petroleum is paraffin, and after 
the distillation of the more volatile portions of the petroleum there 
are left mixtures sold as vaseline, cosmoline, etc., whose consistency 
varies in proportion to the amount of the liquid hydrocarbon left in 
them. Of this class are paraffin and the various forms of petrolatum 
recognized by the Pharmacopoeia. They are all insoluble in water, 
do not become rancid, are free from irritating properties, and act 

* See Ylrchuw's Archiv, 1890, cx\i. 



624 LOCAL REMEDIES 

mechanically on the skin like fats. They are used as local emollient 
applications to the skin and mucous membranes and as a basis for 
ointments. When taken internally in the dose of a drachm to an 
ounce they exert no influence upon the system, but act locally upon 
the mucous membrane of the alimentary canal, allaying irritation 
and provoking soft fecal discharges. 

GLYCEROL. 

Glycerin is a thick, syrupy liquid, colorless, free from odor, and of 
a sweet taste. Chemically speaking, it is propenyl alcohol and is, 
therefore, more correctly called glycerol. It is always set free during 
the process of saponification, and formerly was a by-product in 
the manufacture of soaps. At present it is made by the direct 
decomposition of fats by superheated steam. 

Under certain circumstances, not well understood, glycerin forma 
hard, brilliant crystals. In its usual liquid form it mixes in all propor- 
tions with water and alcohol, and itself dissolves iodine, bromine, 
tannic and other vegetable acids, a large number of salts, and various 
organic principles. It throws, however, most alkaloidal salts out of 
their aqueous solution. 

Glycerin does not evaporate upon exposure, but is very hygro- 
scopic, and absorbs water from the air. When pure, it is incapable 
of becoming rancid or of fermenting spontaneously. The acrid 
glycerin owes its irritant properties to impurities, especially to 
oxalic and formic acids; cheap grades of glycerin are frequently 
contaminated with arsenic. 

Physiological Action. — When large doses of glycerin (in the 
dog eight or more parts per thousand by weight) are injected sub- 
cutaneously, death is produced in a period varying, according to the 
dose, from one hour to several days. The symptoms are loss of mus- 
cular strength, lethargy, bloody urine, vomiting, dryness of the mu- 
cous membrane, with marked thirst, fall of temperature, gradual 
extinction of both respiration and circulation, and finally convulsions 
and coma (Dujardin-Beaumetz and Audije). The convulsions occur 
earlier and are more severe when large doses are employed, and 
are then said to be tetanic, and to be accompanied by a decided rise 
of temperature. The fall of temperature is, even in the milder cases, 
present only late in the poisoning, and is sometimes, if not always, 
preceded by a rise. After death intense congestion, with more or 
less softening of the tissue, is found in the lungs, kidneys, and intes- 
tines. So far as we know, the largest amounts of glycerin taken by 
the stomach in man have produced no other symptoms than those 
of mild gastro-intestinal irritation; but Schellenberg has reported 
a long series of cases in which serious, and in one instance fatal, 
poisoning followed the injection of glycerin containing iodoform, for 
coxitis and other diseases. The conclusion of Schellenberg, that the 
manifestations were due to the glycerin, is confirmed by the fact 



EMOLLIENTS 



625 



that they were those seen in the lower animals poisoned by injections 
of glycerin, —namely, loss of muscular strength, elevation of tem- 
perature, rapid pulse, albuminous bloody urine with tube-casts, ami 
in the fatal case the lesion of acute parenchymatous nephritis. 

Catillon asserts that glycerin administered in small continuous 
doses exerts a decided effect upon nutrition, but the general drift 
of the present evidence is to show that glycerin has no distinct effect 
upon tissue-changes. 

In Catillon's cx]>crimcnts, eight grains given daily to guinea-pigs caused a, 
very marked gain in weight, with a lessened excretion of urea. In man an ounce 
daily also produced a decided diminution in the elimination of urea, which was not 
increased by increasing the doses of glycerin. The appetite in many cases was, 
aftci a little time, much improved, and then the increased ingestion of food produced 
an increased elimination of urea, 'the fact that an increase of food was permitted 
in these experiments shows, however, that the conditions of experimentation were 
not rigid enough to allow much weight to be attached to the result; and the rela- 
tion of glycerin to the elimination of urea has been investigated by L. Lewin, by 
X. Tschirwinsky, and by I. Munk, with somewhat contradictory results. Of these 
experiments the most extensive are those of Munk, who seems to have used all 
proper precautions, and who found that glycerin has no effect upon the elimination 
of urea or upon the general bodily nutrition. The results reached by Lewin corre- 
spond with those of Munk. Tschirwinsky omitted fatty materials from the food, 
and found that while at first the elimination of urea was diminished, it afterwards, 
under the use of very large doses of glycerin, was increased. 

Glycerin is absorbed from the alimentary canal, and when freely 
administered is in part eliminated and in part burnt up in the system. 

Both Ustimowitsch and Plosz found a substance in the urine which they believe 
to be a derivative product of glycerin, while Catillon proved that it is not elimi- 
nated by the skin or, even when it purges, by the intestines. Catillon and Lewin 
recovered from the urine only a small proportion of that ingested, Tschirwinsky 
only 8.7 per cent., while Ludwig Arnschink found that not more than thirty per 
cent, escapes from the body. Since a large proportion of ingested glycerin is oxidized 
in the body, it would appear that it is capable of replacing to some extent true fatty 
carbohydrates for the production of heat or energy, and, therefore, has food value. 
According to the calculations of Arnschink, two hundred and nineteen parts of it 
are equivalent to about one hundred parts of fat. This view is corroborated by the 
work of Scheremetjewsky, who found in rabbits that the intravenous injection of 
glycerin was followed by an immediate increase of the consumption of oxygen, and 
of the giving up of carbonic acid. 

The work of Scheremetjewsky has given rise to considerable 
controversy, but the latest experiments, those of I. Munk, seem to 
lead to the conclusion that glycerin is capable of taking the place of 
the bodily fat.* 

According to Fuchsinger, the bloody urine produced by poisonous 
doses of glycerin contains an abundance of the coloring-matter of 
the blood, but no free corpuscles. Very interesting in connection 
with the use of glycerin in diabetes is the assertion of Fuchsinger, 
that in rabbits slightly poisoned with glycerin no sugar appears in 



40 



* For discussion, see Archiv f. d. Ges. Phys., 1889-90, .xlvi 



626 LOCAL REMEDIES 

the urine after the "diabetic puncture." The experiments of Eck- 
hard gave, however, a contrary result, and Catillon affirms that given 
in very large continuous doses glycerin increases the amount of sugar 
in the blood. 

Therapeutics. — Locally applied, glycerin is usually unirritat- 
ing, and it is much employed as an emollient. The chief disadvantage 
that attends its use is its stickiness; on the other hand, its non- 
volatility and its hygroscopic properties give a persistency to its 
action which is often very advantageous. It enters largely into the 
composition of popular emollient ointments, or "creams," as they 
are called, and is often used itself for chapped hands, excoriations, and 
similar troubles. It is also employed by dermatologists to some 
extent in chronic eczema; in seborrhea, whether affecting the hairy 
scalp or other parts, it is asserted to be especially useful, softening 
the masses of secretion, and, used in conjunction with such remedies 
as borax, zinc, and lead acetate, diminishing the amount of secretion. 
When there is a want of sebaceous secretion, it is said also to act 
efficiently; in scabies, pruritus, and even psoriasis, glycerin is used, 
diluted with water, as a vehicle for more active remedies. Upon 
the mucous membranes glycerin acts very much as it does upon the 
skin, and diluted with water is very useful in coryza, and even, by 
.enemata, in dysentery; in croup or laryngitis it may with advantage 
be applied freely by means of a large camel's-hair brush to the orifice 
of the larynx, so as to run into the latter. In laxative doses it is 
asserted to be very effective in hemorrhoids. It also forms an excel- 
lent basis for mouth-washes; or a paste may be made with it and 
borax, or similar substance, for use in ulcerations of the same cavity. 
The list of diseases in which this remedy is employed might be very 
much lengthened; but the examples already given are sufficient to 
indicate the range of its application as an emollient and as a vehicle. 
There are certain persons upon whose skin and mucous membranes 
even the purest glycerin seems to act as an irritant. This influ- 
ence is most intense when the glycerin is nearly or entirely free 
from water. It is, however, discernible even when the remedy is 
much diluted, and often inhibits its use. The existence of this 
idiosyncrasy to glycerin can be determined only by trial. 

When administered internally in doses of one or two ounces, 
glycerin acts as a gentle but very uncertain laxative. It was proposed 
many years ago as a substitute for cod-liver oil in cachectic diseases, 
but has failed to come into use. It has also been highly commended 
in diabetes * but is of no service. It is valuable as a harmless sub- 
stance which has the power of disguising nauseous medicines. In 
this way it may be employed with castor oil, in emulsions of tur- 
pentine, in solutions of iron, and in various mixtures. It seems as it 
were, to envelop the medicinal substances and prevent their acting 
on the palate. 

* For literature anil discussion of point, see Ziemsaen's Encyclopaedia, xvi. 



EMOLLIENTS 



627 



BENZOSULPHINIDE. 

Saccharin* is a BUbstance discovered by Kahlbergin 1879. Chemi- 
cally it is an imide derived from the toluene of coal-tar. It occurs as 
a white powder composed of irregular crystals, very slightly soluble 
in water, readily soluble in glycerin, alcohol, and ether. Its watery 
solution lias a distinctly acid reaction, and it forms salts. Its most 
remarkable property is its sweet taste, which is said to be three 
hundred times more intense than is that of sugar, so that if one grain 
of it be dissolved and neutralized in about ten pints of water its 
presence can still be recognized. Taken internally, saccharin is 
rapidly absorbed; it is eliminated unchanged chiefly through the 
kidneys. Bruylants having recovered about eighty per cent, of it 
from the urine. It has been found by Bruylants in the milk of a 
nursing woman, and by Hedley abundantly in the saliva. Its influ- 
ence upon man and animals is very slight; Mosso and Aducco admin- 
istered seventy-five grains to a man without sensible effect, and found 
that frogs will live for months in a solution rendered neutral with 
soda; also, that six hundred grains given to a dog during ten days 
caused no change in the daily renal excretion of water, urea, hippuric 
acid, sulphuric acid, or phosphoric acid, and no alteration of the 
weight or of the general health. On the other hand, it appears to 
have a feeble influence upon various fermentations. Its solution has 
antiseptic properties, and in Plugge's numerous experiments it checked 
the action of ptyalin, pepsin, trypsin, and other allied ferments. 
Sawitzki, indeed, alleges that it depresses proteid metabolism. In 
Bruylants's trials it failed to check artificial gastric digestion, prob- 
ably on account of the acidity of the solution, but as little as one per 
cent, is enough distinctly to lessen the activity of pancreatin solu- 
tions. The general innocuousness of saccharin is, in accord with our 
own experience, asserted by Salkowski, by Bruylants, by Dresch- 
feld, by Levenstein, and by other clinicians. Mixed with sodium 
bicarbonate, two parts to three, saccharin becomes soluble. Its chief 
value in practical medicine is as a substitute for sugar in diabetes, 
obesity, and other diseases in which sugar is contraindicated, but the 
observation of James Little, that when freely given it is of great 
antiseptic value in the treatment of ammoniacal urine, from cystic, 
prostatic, or other diseases producing retention or fermentation, 
is probably correct. It may be used freely as an article of diet, in 
the form of a solution in glycerin; for medical purposes it is sometimes 
administered in compressed pills: dose, five grains (0.3 Gm.). 

Kaolin. — Porcelain Clay. — Fuller's Earth is a white powdery 
clay, unctuous when moist, a hydrated aluminum silicate. It is 
largely used in the arts for the purpose of clarifying and decolorizing 
oils and other fluids. It is a non-irritant, inert substance, which is 



* The present is probably as good as any other place in this treatise to notice a substance 
whose use in practical medicine depends upon its lack of medicinal properties. 



62S LOCAL REMEDIES 

well fitted for thickening ointment or paste. It enters into the official 
Cataplasma Kaolini, U. S., Cataplasm of kaolin, a thick, paste- 
like substance containing 57.5 per cent, of kaolin, 4.5 per cent, of 
boric acid, .05 per cent, of thymol, .2 per cent, of methyl-salicylate 
and 0.5 per cent, of oil of peppermint, held together with 37.5 per 
cent, of glycerin. A vast amount of nonsensical rubbish has been 
written and believed of the virtues of this paste. It possesses how- 
ever no virtues that do not belong to the flaxseed poultice and is 
probably even less efficient. 

Poultices. — Poultices are moist, soft, scarcely adhesive, per- 
fectly bland plasters, used to a very great extent to combat super- 
ficial inflammation. Poultices are much more powerful agents than 
are the true fatty emollients, and are correspondingly more capable 
of being abused: the results of such abuse will be spoken of directly. 
A poultice may, of course, be stimulating and irritant if made of such 
a substance as mustard; but the ordinary emollient or true poultice 
is prepared out of some bland material which is totally free from action 
upon the skin, and depends for its remedial power solely upon the 
warmth and the water which it contains. Water, when pure and of 
a temperature approximating that of the body, is a sedative, checking 
all action, possibly by a direct influence, but probably by the merely 
mechanical acts of dilution of the pabulum and of separation of the 
germinal granules. It is also a relaxant, rendering all tissues soaked 
in it soft and yielding. 

Poultices are sometimes applied in the early stages of phleg- 
monous and other superficial inflammations, for the purpose of check- 
ing the morbid action. Their influence is in such case simply one of 
sedation, and they are certainly not so efficient as the cold-water 
dressing. They are, however, especially useful in the advanced stages 
of inflammation, when suppuration has already commenced or is 
about to set in. Clinical experience has demonstrated that the}' 
then favor the formation of pus. Further, the poultice in the latter 
stages of a superficial phlegmon not only hastens the formation of pus 
in the inflammatory focus, but lessens irritation in the outlying parts 
by its sedative action, and so softens the tissues as to aid in the 
passage outward and the discharge of the inflammatory products. 
When poulticing is too long persisted in, the part becomes pale or 
white, swollen, relaxed, and has a sodden look; the granulations of 
the ulcer or abscess are large, pale, and very flabby, and all the vital 
actions are below the normal point. It is possible that even death 
of a part might be brought about bj r continuous poulticing. Be 
this as it may, after the discharge of pus, whenever the parts put on 
the aspect just spoken of, the poultice should be removed and 
stimulating applications substituted. 

Any material which is in itself physiologically inert, and will 
long retain water, may be used as the basis of the poultice. Flax- 
seed meal is cheap, and is probably the most used of any substance. 



EMOLLIENTS 



(>'_>!> 



Ground slippery elm makes :i very elegant mucilaginous poultice. 
Ordinary Indian- meal mush is often used. The bread and milk poultice 
is non-irritating, but is prone to undergo putrefaction. The poultice 
is rarely aseptic, and is often a carrier of germs. This in a measure 
may be prevented by boiling the poultice just before putting it on; 
but even with this precaution, when applied to an infected wound, 
poultices, by retaining and stimulating the growth of germs, often 
increase the inflammation. For this reason other methods of apply- 
ing warmth and water have largely replaced the old-fashioned poul- 
tice. Spongiopiline, or absorbent cotton, or similar material, which 
is readily rendered aseptic, ami is incapable of undergoing fermenta- 
tion, when saturated with heat and water affords an application 
which is practically a poultice, and which may be rendered germicidal 
by the addition of minute quantities of corrosive sublimate or similar 
substances, as called for by the exigencies of the case. 

Poultices are frequently used in the treatment of deep-seated 
inflammations. Under these circumstances, according to the dic- 
tates of experience, they should be applied very hot, and be frequently 
renewed; very often, too, a small amount of mustard or of some 
similar stimulating material is added to them with advantage. As 
a result, these poultices act as gentle but deep-reaching counter- 
irritants, which in all likelihood affect not merely the blood-vessels 
of the skin, but also those of the subdermal tissue. When it is borne 
in mind that in all these cases the poultice is applied to a very large 
surface, it will readily be perceived that this counter-irritation is a 
powerful one. Thus, in pleurisy or in pneumonia the whole anterior 
or posterior surface of the chest is covered, or perhaps the whole chest 
is enveloped, by the jacket-poultice. In peritonitis the poultice 
should be as large as the abdomen of the patient. In either of these 
cases the amount of blood drawn to the surface must be considerable. 
It is probable that the water of the poultice in some cases actually 
soaks through and exerts its direct sedative influence upon the affected 
tissue. The value of poultices in lung diseases is much greater in 
children, whose chest-walls are very thin, than in adults; and it is 
not illogical to believe that the difference may be dependent upon 
the inequality of the chest-walls. 

The jacket-poultice should be made of thin flannel formed into a sort of double 
bag, so cut and shaped as to fit the individual, and secured in front with safety-pins 
and over the shoulders with tapes, or it may be fastened directly to an undershirt, 
a piece of oiled silk always being placed directly outside of the jacket. The jacket 
should be divided into two parts by a horizontal line of stitching, and be filled from 
one end. In order to prevent sagging of the contents, it is well, after filling, to 
take a stitch here and there, in the manner of quilting. The effect of a jacket- 
poultice may be imperfectly attained by covering the patient with wool batting and 
oiled silk outside of this, — in fever patients the moisture from the surface and the 
heat of the body serving to form a kind of fomentation. 

The value of the jacket-poultice in disease is, however, greatly 
lessened by the fact that it enormously increases the heat-retention 



630 



LOCAL REMEDIES 



of the body, and has, therefore, in many cases a very serious influ- 
ence in heightening a fever temperature whose reduction is urgently 
indicated. Whenever, in a pneumonia, the temperature is high, the 
application of cold water by means of compresses, or absorbent 
cotton, is preferable to the use of the jacket-poultice. In cases of 
'peritonitis the sensations of the patient are often a practical guide 
to the choice of the dressing. If the pain is aggravated by external 
warmth, the cold-water dressing is preferable; while, if the cold- 
water dressing is steadily obnoxious to the patient, the best results 
may usually be achieved by the use of hot water. 

Collodion. — This is a solution in alcohol and ether of pyroxylin 
or soluble gun-cotton, which consists chiefly of the tri- and and tetra- 
nitro-cellulose; upon evaporation collodion leaves on the skin an 
adherent protecting film. 

Physiologically, gun-cotton is inert. Collodion is a colorless, 
slightly opalescent liquid, of a syrupy consistence, and smelling 
strongly of ether. By long standing it deposits a layer of fibrous 
matter, and becomes more transparent. This layer should be rein- 
corporated, by agitation, before the collodion is used. When it is 
applied to the skin, and the menstrua are allowed to evaporate, 
collodion forms an impervious, colorless, transparent, flexible, and 
strongly contractile film, which adheres very closely, and cannot 
readily be removed. The contractility of the film may in a great 
measure be destroyed by the addition to the collodion of certain 
substances, as in flexible collodion, which contains five per cent, 
of Canada turpentine and three per cent, of castor oil, and on 
evaporation leaves a film which does not contract. 

As a substitute for collodion the non-official solution of gutta- 
percha in chloroform {Liquor Gutta-Perchce) is sometimes employed. 

Official Preparations : 

Collodium External use. 

Collodium Flexile External use. 

Collodium Cantharidatum (Cantharides 60 per cent.) External use. 

Collodium Stypticum (Tannic Acid 20 per cent.) External use. 



REFERENCES. 

Arnschink Sitzungsb. Gesellsch. Mor. Kaspar 

phol. Phvsiol., Miinchen, Levenstein. . . 

1886, ii.; Z. B., xxiii. 413. Lewin 

Bruylants B. A. R. B., 1888. Little 

Catii.lon B. G. T., xcii. 130; A. de 

P., 1877. Monk 

Dreschfei.o Birmingham Med. Journ., Patschkowsky 

1880, 409. Pi.6sz 

Dujardin-Beaumetz and Audije..B. G. T., Rosenberg... 

xci. 62. Salkowski 

ErKHARD CM. W., 1876, 273. Schellenberg 

Fuchsincer A. G. P., xi. 502; A. G. P., Tschirwinsky. 

xii. 501; C. M. W., 1877. Ustimowitsch. 



. . D. M. W., Dec. 1885. 

. .Journ. Soc. of Chem., 1886. 

. Z. B., xv. 

. .Trans. Royal Acad, of Med., 

Ireland, 1888, vi. 
. .V. A. P. A., lxxvi. 130. 
. .Pharm. Zeit., 1885. 
..A. G. P., xvi., 153. 
. .S. Jb.. 1890. 
. .V. A. P. A., cv. 46. 
..A. K. C, 1894, xlix. 
. .Z. B., xv. 
..A. G. P., xiii. 453. 



DIVISION II. — EXTRANEOUS 
REMEDIES. 



These are drugs which are employed not to act directly upon the 
human system or upon any of its tissues, but upon some extraneous 
material or entity , either in the cavities of the body or upon its exterior. 
Thus, an antacid neutralizes acid in the stomach, or an anthelmintic 
kills the tapeworm in the intestines, or a disinfectant destroys poison- 
ous emanations in the exterior world and thereby wards off disease. 



FAMILY I.— ANTACIDS. 

Antacids are, strictly speaking, substances which are capable 
of neutralizing acid. The class, as here defined, contains those reme- 
dies which in medicine are used for the purpose of neutralizing an 
excess of acidity in the primse viae. They are almost solely employed 
in forms of dyspepsia. Without doubt, cardialgia, gastric uneasiness , 
heartburn, and the rising of sour water in the mouth are often the 
result of too much acid in the stomach, perhaps secreted by a per- 
verted glandular action, but more probably in the great majority 
of cases formed by fermentative changes in the partially digested 
food. As excessive acidity of the stomach causes gastric uneasiness 
and derangement, so will a similar condition of the intestinal canal 
cause pain and spasm and functional disturbance in the bowels. 
This is seen most frequently in infants, and is very often associated 
with a diarrhoea in which the passages have a green color, similar to 
that of spinach, and hence are sometimes spoken of as "spinach- 
stools. " In diarrh&a of this character, as well as in colic, antacids 
are often of service by neutralizing the acid in the intestinal canal. 

Clinical experience has demonstrated that dyspepsia is often 
permanently relieved by the use of alkalies when they are given 
steadily day after day, for a long time. According to Thomas K. 
Chambers, this is dependent upon an effect pointed out by Claude 
Bernard, — the augmentation of the acid gastric juice, and so of the 
normal peptic powers of the stomach. The same authority further 
says, "The test of benefit being derived from an alkali is the dose not 
requiring to be increased as the patient goes on taking it, but, on 
the contrary, being diminished gradually, while relief from the 
recurrence of heartburn continues still to be experienced." 

631 



632 EXTRANEOUS REMEDIES 

Sick headache is sometimes dependent upon gastric irritation 
produced by an excess of acid in the stomach. This true sick head- 
ache is generally to be distinguished from migraine by the early 
occurrence of the stomach symptoms, either as heartburn, nausea, 
vomiting, or simple gastric distress, and by the fact that the pain 
comes on with an attack of blindness or of dizziness, and is not limited 
to any one spot, as the supra-orbital or other neuralgic foci, but is 
felt all across the brows. In this form of cephalalgia antacids often 
afford prompt relief. 

Various substances which have already been discussed in this 
work are excellent antacids, most of them uniting this to other medici- 
nal properties. Thus, when a stimulating antacid is desired, as is 
very often the case ki sick headache, half a drachm of the aromatic 
spirit of ammonia may be taken, well diluted with water. Potassium 
and its carbonates have already been dwelt upon with sufficient 
detail. They may be used as antacids; but, as they exert other 
powerful influences upon the system, they are, we think, not so 
generally useful as the soda preparations. 

SODIUM. 

The alkaline salts of sodium include the hydroxide, carbonate 
and bicarbonate. 

Sodium hydroxide is usually found in the form of white or nearly 
white sticks or pencils which deliquesce and subsequently absorb 
carbonic acid. 

Sodium carbonate is found commercially united with various 
proportions of water of crystallization. The Pharmacopoeia recog- 
nizes only the mono-hydrated sodium carbonate; this is a white 
crystalline granular powder without odor but with a strongly alkaline 
taste. It is soluble in 2.9 parts of water and insoluble in alcohol. 

Sodium bicarbonate is a white odorless powder with a mildly 
alkaline taste soluble in 12 parts of water at 59° F. At higher tem- 
peratures it gradually loses carbonic acid and is changed into a 
carbonate. It gives a slightly alkaline reaction with litmus. 

Official Preparations : 

Sodii Hydroxidum [Caustic Soda] Not used internally. 

Liquor Sodii Hydroxidi (5 per cent.) 15 minims (1 C.c). 

Sodii Carbonas Monohydras [Washing Soda].. 5 to 10 grains (0.3-0.6 Gm.). 
Sodii Bicarbonas [Baking Soda] 10 to 20 grains (0.6-1.2 Gm.). 

Soda * being the normal alkali of the blood, even very large doses 
of it have very little influence upon man or mammalia, but it is 
probable that it acts much more powerfully on cold-blooded animals. 

Grandeau found that one hundred and seven grains of sodium carbonate 
injected into the vein of a dog produced only very slight symptoms, and that thirty- 

* As Rabuteau found that in dogs with gastric fistula both the quantity and the acidity of 
the gastric juice are decidedly increased by the use of salt meat, it would appear probable that the 
local action of common salt upon the stomach is that of a stimulant. 



ANTACIDS 633 

live grains of the nitrate similarly administered to a rabbil caused only some con- 
vulsive movements. According to Guttmann, however, the sodium salts thrown 
directly into the blood in very large amounts will slowly cause death, the agony 
being very prolonged, and, when the chloride is used, convulsions being developed. 
Hoth Podocaepow and Guttmann asserl that, even the largest doses do not, sensibly 
Bffed tin- heart or I he temperature; and the latter observer further declares that 
they are without influence upon the nerve-centres, the peripheral nerves, or the 
muscles. Hut if this be the case, it is difficult to perceive how they can cause death; 
and the earlier experiments of Podocaepow indicate that they do exert a very 
feeble action upon the peripheral nerves or the muscles. Curci also finds that the 
sodium salts increase the blood-pressure alter the destruction of the oblongata, 
and believes that they influence the peripheral vaso-motor nerves. II. (1. Beyer, 
BS the result of experiments made upon terrapins, conies to the conclusion that 
sodium salts excite first the ganglia of the vaso-dilator nerves and afterwards those 
of the vaso-constrictor nerves. 

Although Mayet affirms that sodium chloride increases the elasticity of the 
red blood-corpuscles, the immediate influence of the sodium salts upon the blood * 
is probably very slight, since, according to Podocaepow, one part dissolved in twelve 
parts of blood does not affect either the physical characters of the red corpuscles 
or the intensity of the ozone reaction. 

Podocaepow and Schonlein both affirm that they cause in the frog spinal con- 
vulsions, but in Ringer and H. Sainsbury's experiments the influence of the sodium 
salts upon the frog was found to be so slight that they could hardly be made to 
kill. It seems established, however, that they will produce cataracts in the frog.f 
Most observers state that the sodium salts are capable of arresting the frog's heart 
in diastole, either when it is in position or after it is removed from the body; and 
Laffout states that there is a primary period of cardiac stimulation, which is in 
accordance with the observation of T. W. Mills upon fishes. There is, however, 
much difference of statement by different observers in regard to the action of these 
salts upon the frog's heart. J 

Nutrition. — A certain amount of soda is a necessary food for the 
higher animals, yet it is very doubtful whether an habitual excess 
has decided effect upon the nutrition, the general drift of the present 
evidence being to show that when in excess the sodium salts neither 
increase nor yet decrease the elimination of. urea or other products 
of tissue-waste. 

In the experiments of Munch the continuous exhibition of large doses of com- 
mon salt to man apparently produced at first a slight diminution of excretion and a 
corresponding gain of the body in weight; but after a time the excretion increased 
and the weight of the body decreased. The variations in excretion affected chiefly 
the urine, but sometimes the perspiration and feces were also influenced. The 
urine was rendered alkaline, but its solid ingredients were scarcely at all affected. 
The conclusion of Damourette and Hyades, that salt increases the elimination of 
urea and uric acid, is not warranted by their own experiments; and in the researches 
of I. Mayer, of A. Ott, of C. Clar, and of L. Klemptner, neither the sodium citrate, 
acetate, phosphate, or sulphate increased nitrogenous elimination, while in those 
of Dalebe and Carberet the alkaline sodium salts reduced the output of urea. 

* Kowalewsky records in the Centralbl. f. Med. Wissen., 1887, the results of an elaborate 
study of the effects of adding, either in solid form or in concentrated solution, salts of potassium, 
sodium, lithium, and ammonium to the blood. As it is not possible at present to connect this 
influence with the effects of therapeutic doses of the drug inside of the body, we content ourselves 
with referring to the paper. 

t For a discussion of this, and literature on the subject, see Limbcurg (Arch. /. Exper. Path. 
u. Pharm., 1888, xxiv.). For a series of papers on the antagonistic actions of sodium, potassium, 
and calcium salts on the frog, by Sydney Ringer, see Journal of Physiology, 1890, 1894, 1895. 

% See Podocaepow (Virchow's Archiv, xxxiii. 507), Schonlein (Arch. f. d. Ges. Physiol., xviii. 
26), Laffout (Compt.-Rend. Hoc. Biol., 1880, 282), Ringer and Sainsburv (Lancet, 1882, ii. 73li), 
Ringer (Brit. Med. Journ., 1884), I.imbourg {Arch. /. Exper. Path. u. Pharm., 1888, xxiv.). 



634 EXTRANEOUS REMEDIES 

Therapeutics. — The fact that soda, in moderate amount, 
has no depressing action, and indeed very little, if any, influence 
upon the general system, renders it preferable to potassium in cases 
of acidity of the primae viae. It is par excellence the alkali for acid 
dyspepsia. On the other hand, the circumstance clearly established 
by Roberts, that it is less powerful as a solvent of uric acid than is its 
sister alkali, together with the property, believed to belong in a much 
greater degree to potassium, of preventing the formation of uric 
acid, makes sodium of very inferior value in uric acid gravel or uric 
acid diathesis. When in any case it is desirable simply to render 
the urine alkaline, and at the same time to avoid depressing the system 
generally, soda would, on theoretical grounds at least, seem preferable. 

It appears to be well proved, clinically, that the alkaline sodium 
salts given one to two hours before meals in full doses are of decided 
value in the treatment of chronic hepatic torpor, of catarrhal jaun- 
dice, and especially of gall-stones or other affections associated with 
excessive viscidity of the biliary secretions. 

As the result, however, of an elaborate series of experiments made upon dogs 
with biliary fistula, J. Glass concludes that the alkalies given by the mouth do not 
increase the alkalescence or amount of the bile. The caution necessary in apply- 
ing such experiments to human medicine has been spoken of in an earlier chapter. 
Moreover, it was apparently proved by the experiments of S. W. Lewaschen that 
the sodium carbonate, sulphate, or phosphate, given to dogs with biliary fistula, 
increases very markedly the liquidity of the bile by diminishing the percentage of 
solids. The sodium salicylate acted similarly to, but much more powerfully than, 
the other salts. E. Dufourt, experimenting with the sodium bicarbonate upon 
dogs, found that there was a very constant and pronounced increase both of the 
glycogen and of the sugar of the liver. 

A possible therapeutic use of sodium carbonate is suggested by 
the experiments of W. H. Howell, who found that in the lower animals 
intravenous or rectal injections of solutions of sodium carbonate 
increase markedly in animals suffering from shock the amplitude of 
the heart-beat, and cause a rise of arterial pressure. Dalebe and 
Carteret affirm that in diabetes, especially of the azoturic form, sodium 
carbonate is a very valuable remedy. 

Although so harmless, the sodium salts when in great excess are 
decidedly irritant, and it has been shown by Stokvis and Levi 
that it is possible with the sodium chloride to produce albuminuria, 
tube-casts, and organic renal changes. 

As an antacid the bicarbonate should usually be selected, as 
being the least irritant. 

MAGNESIA. 

The heavy and the light magnesia differ only in their physical 
characters, the particles being differently aggregated. Magnesium 
carbonate is manufactured by precipitating a solution of magnesium 
sulphate by one of sodium carbonate. If the two solutions be con- 
centrated, the dense or heavy carbonate will fall; on the other hand, 



ANTACIDS 635 

if the solutions be dilute, the precipitate will be a light carbonate. 
Heavy magnesia is obtained by calcining a heavy carbonate; light 
magnesia, by using a lighl carbonate. All of these substances are 

of a milk-white color, and occur in powder; the carbonates sometimes 
in very light cubical blocks. They are all practically insoluble in 
water, freely soluble in dilute acid, and in the presence of acids they 
all act as alkalies. 

Official Preparations : 

Magnesii Oxidum [Calcined Magnesia] l to 4 drachms (4-15 Gm.). 

Magnesii Oxidum Ponderosum 1 to 4 drachms (I l"> Gm.). 

tfagnesii Carbonas I t<> I drachms ( I l"> Gm.). 

Therapeutics.— Magnesia ami its carbonate are antacid and 
laxative, for their purgative powers they are probably dependent 
upon the presence of acids in the prima? wise, and hence their effects 
vary. When taken repeatedly they are said at times to accumulate 
in the intestines, and should not be used as an habitual laxative. 
They are often given along with Epsom salt or senna, on account of 
their antacid properties. Their chief use is in acute acid dyspepsia, 
in skk headache, in diarrhoea with excessive acidity in children, in 
gout, in rheumatism, and in various cutaneous affections, — wherever, 
in a word, a laxative antacid is indicated. 

CALCIUM. 

Of the numerous salts of calcium there are considered here only 
those in which the action of the basic ion predominates. These are 
the oxide, the carbonate, and the chloride. 

Calcium oxide, or lime, is made by calcining the carbonate, and 
occurs as white or grayish white masses which when exposed to the 
air absorb carbonic acid and crumble to a white pow r der. When 
moistened with about one-half its weight of water there is formed 
with the evolution of much heat, a white powder, calcium hydroxide 
or slaked lime. Lime is soluble in 760 parts of water at 77° F. but 
becomes less soluble as the temperature of the water is raised, so that 
boiling water will dissolve but one part in 1600. 

Calcium carbonate is a very widespread natural salt, being the 
basis of marble, chalk, and Iceland spar. The U. S. Pharmacopoeia 
recognizes two forms of calcium carbonate, namely, prepared chalk 
and the precipitated calcium carbonate. Each of these occurs 
as a white powder practically insoluble in water, although small 
quantities may be dissolved in solutions of carbonic acid. 

Calcium chloride is seen in the form of white semi-translucent 
fragments, odorless but with a sharp saline taste. It is soluble in 
1.3 parts of water and 8 parts of alcohol, and is extremely deliquescent. 

Calcium sulphate, or plaster of Paris, is a fine white powder with 
a faint earthy odor, which is prepared by heating gypsum until most 
of the water is expelled. It is used in medicine for purely mechan- 
ical purposes. It absorbs water and in a few minutes solidifies. 



636 EXTRANEOUS REMEDIES 

Official Preparations : 

Calx [Calcium Oxide: Lime] Not used internally. 

Liquor Galcis [Lime Water] (0.14 per cent.). . 1 to 4 fluidrachms (4-15 C.c). 

Syrupus Calcis (6.5 per cent.) 10 to 20 minims (0.6-1.2 C.c.). 

Liniment um Calcis [Carron Oil] External use. 

Calcii Carbonas Pra'eipitatus 15 to 60 grains (1^1 Gm.). 

Creta Praparata [Prepared Chalk] 15 to 60 grains (1-4 Gm.). 

Pulvis Cretan Compositus (30 per cent.) \ to 1 drachm (2—4 Gm.). 

Mistura Cretan (6 per cent.) i to 1 fiuidounce (15-30 C.c). 

Calcii Chloridum 10 to 30 grains (0.6 1 Gm.). 

Calcii Sulphas Exsiccatus [Plaster of Paris]. .Not used internally. 

Local Action. — Unslaked lime is an active escharotic; slaked 
lime is an irritant, or, when in concentrated form, a feeble escharotic. 

Absolution and Elimination. — Lime is never used in substance in 
medicine, but in the form of a aqueous solution. When in such dilute 
form it acts as a detergent and sedative, especially to mucous mem- 
branes. Its official insoluble preparations are free from irritant 
properties and are mild astringents. Neither the soluble nor insoluble 
preparations of lime are absorbed to any large extent, the lime escap- 
ing, if given in considerable dose, in great part with the feces in 
the form of some insoluble salt. Minute quantities of it probably 
circulate in the blood in combination with proteids. 

When a soluble salt of calcium is given intravenous^, an insoluble 
form of lime is probably rapidly deposited in the tissue. Excretion 
of lime chiefly takes place through the urine, or perhaps more largely 
through the large intestine. 

Physiological Action. — Probably owing to the difficulty of 
their absorption, even the soluble preparations of lime have not been 
found in practical medicine to have any general effect upon the body. 
Carl Franke, indeed, states that the intravenous injection of large 
amounts of soluble lime salts has no effect upon rabbits. 

The soluble salts of lime are evidently not without physiological activity, and 
have close relation with the general bodily well-being. W. H. Howell and E. Cooke 
have proved that the inorganic salts of the blood, milk, gastric juice, etc., are able 
to keep the isolated frog's heart beating with force and regularity for many hours 
without other food, and, according to the experiments of Ringer, among these 
salts those of lime are especially important. Further, it seems to be demonstrated 
that small doses of soluble calcium salts increase the energy of the heart's action, 
as the experiments of Ringer have been confirmed by Mickwitz and also by Binet. 
Langendorff and Hueck believe that their own and previous experiments justify 
the conclusion that the presence of calcium in the nourishing liquid is absolutely 
essential for the continuance of the cardiac action, not only in cold but also in 
warm-blooded animals. Binet states that though the cardiac arrest usually takes 
place in systole in calcium-salt poisoning, yet if the salt have come directly in con- 
tact with the heart in concentrated form there is paralytic arrest (diastolic). Further, 
according to Ringer and to H. G. Beyer, the voluntary and involuntary muscles of 
the frog are stimulated by small amounts of calcium; and, according to Franke, 
they are paralyzed by large amounts of the drug. Stefani states that calcium chloride 
when applied locally in minute amount increases the functional activity of the 
motor nerve-trunks, but when in large amount produces rapid paralysis; while 
Binet has demonstrated that the toxic dose of the calcium salt directly paralyzes 
the cerebral cortex and the motor centres of the spinal cord. 



ANTACIDS 637 

It is certain that the calcium sails are essential to all the higher 
tissues. It is probable that under ordinary circumstances a suffi- 
ciency oi these salts is furnished to the system by the food, and that 
no gain is to be achieved by their further administration. This is, 
however, only a probability, not a definitely demonstrated fact; 
it may be that the soluble haloid salts have more practical value 
than is at present believed. 

Therapeutics. -As antacids the salts of lime are used largely 
in the treatment of diarrhoeas, not only because none of the calcium 
salts are laxative but also because they seem to exercise a mildly 
astringent influence.* For this purpose one of the preparations of 
the carbonate is generally preferred, although the syrup of lime is 
occasionally employed. 

In vomiting, from almost any cause except acute gastritis, equal 
parts of lime-water and milk afford an elegant, simple, and much- 
used remedy. If the vomiting be severe, all other food should be 
inhibited, and one or two tablespoonfuls of the mixture given every 
half-hour, — the quantity, as well as the proportion of milk, being 
increased as the stomach is able to bear it. As lime-water when put 
in milk prevents the formation of dense coagula, it is often added 
with advantage to that fluid when used as food for infants, or for 
adults with weak digestion. 

Externally, lime-water has been used as a wash in various skin 
diseases, especially in tinea capitis: it is also applied to ulcers, and is 
said to have a very marked influence in lessening the amount of 
discharge. When mixed w r ith an equal bulk of linseed or olive oil 
lime-water forms a thick, soapy liquid (Carron Oil, so called from the 
name of the iron-works at which its reputation was first made), which 
is much used in recent burns. 

Lime-water has the power of dissolving mucus and also false 
membrane, and has therefore been introduced as a local remedy in 
pseudo-membranous croup and in diphtheria. It is sometimes used 
by causing the patient to inhale the vapors of slaking lime, but a 
better method is to pulverize lime-water by means of an atomizer 
and direct the spray upon the back of the fauces while the patient 
is respiring deeply. The application should be made every two or 
three hours. 

Externally, prepared chalk and precipitated calcium carbonate 
are used as desiccants and protective applications to ulcers and 
chronic burns, also in excessive sweating of the feet, and in intertrigo 
and other affections of the skin. 

Calcium Chloride is locally a violent irritant, but it is strongly 
recommended by See in the treatment of gastric catarrh and fermenta- 
tive dyspepsia. The results of experimental studies as to the action 

* J. Bruce MacCallum (University of California Publications, Vol.i., — confirmed by Ott) has 
found that calcium chloride very markedly inhibits peristalsis in the rabbit, and suggests its use 
in nervous diarrhma. 



63S EXTRANEOUS REMEDIES 

of calcium chloride upon the heart suggest the probability that when 
hypodermoclysis is indicated in conditions involving also cardiac 
failure, the addition of chloride of calcium to the normal saline 
solution might be of great service. 

Calcium chloride is also largely used in the treatment of internal 
hemorrhage with the idea that it increases the coagulability of the 
blood. While there is some evidence that, when injected into the 
vessels directly, it has such an action, it is probably not absorbed 
from the intestinal tract in sufficient quantity to exercise any 
marked influence. 

REFERENCES. 

Beyer M. News, Sept. 4, 1886. Levi Centralbl. f. Allg. Path. u. 

Beyer M. News, Sept. 1886. Path. Anat., 1895, vi. 

Binet R. M. S. R., 1892. Mayer Z. K. M., 1881, 82. 

Chambers The Indigestions, Am. ed., Maykt C. R. S. B., 1897, 10 s., iv. 

1870,67. Mills Canada Med. Surg. Journ., 

Clar C. M. W., 1888, xxiv. March, 1886. 

Curci L. M. R. Oct. 15, 1886. Munch Arch. d. Vereins f. Gemein. 

Dalebe and Carteret. .B. G. T., Nov. 1901. Arbeit., 1863, vi. 369. 

Damourette and Hyades. .J. de Th., 1880, Ott H. S. Jb., 1883, 220. 

440. Ott Ott's Contributions to 

Franke Thesis, Wurzburg, 1889. Physiology, part 16, 1905. 

Glass A. E. P. P., 1892, xxx. Rabuteau L'Union Mdd., 1871, xii. 

Grandeau J. de PA. P., 1864. _ „ 186. ... 

Guttmann V. A. P. A., xxxv. Podocaepow \ . A. P. A., xxxin. 507. 

HowELt c °y\ Med - Researc ^ r1noer: ::::::::: n.y. m. r 1 .; xx Xi . 

, _ T ug £ al \ no ■ Ringer and Sainsbury. . L. L., 1882, ii. 736. 

Howell and Cooke. .J. P., 1893, xiv. Roberts Urinary and Renal Diseases, 

Klemptner Thesis, Dorpat, 1889. Am ed 1866 240 

Laffout C. R. S. B., 1880, 282. Schonlein A. G. P., xviii. 

Langendorff and Htjeck..A. G. P., 1903, Stefani A. I. B., 1894, xxii. 

xcvi. Stokvis A. E. P. P., xxi. 



FAMILY II.— ANTHELMINTICS. 



THESE are medicines which kill or cause the expulsion of intestinal 
worms. They are sometimes divided into vermicides, those which 
kill, and vermifuges, those which expel; but there is little or no prac- 
tical use in the division. It is of much greater importance to establish 
the relations between these drugs and the different species of entozoa, 
since clinical experience has demonstrated that an anthelmintic very 
efficient against one form of intestinal worm may be not injurious to 
another species. Therapeutically considered, the entozoa may be 
divided into the Tapeworms (Tcenice), the Round-worms (Lumbrici), 
and the Seat-worms (Ascarides). The last of these differ from the 
others in that they are to be attacked solely by enemata. 

It is obvious that the value of an anthelmintic depends not only 
upon its power of poisoning the articulate, but also upon its harmless- 
ness as regards the patient. Thus, it is the eminent combination of 
these qualities that renders the infusion of quassia so valuable in 
cases of seat-worms, while phenol, though very efficient, should 
never be used against the same parasite, since it has greatly imperilled, 
if it has not destroyed, the life of the patient when so employed. 

There are certain general rules which govern the administration 
of anthelmintics, and which should not be lost sight of. They may 
be summed up as follows: 

Let the alimentary canal be as empty as possible, so that the drug 
may act with the greatest force upon the enemy. For this reason, 
anthelmintics are best administered early in the morning; and in 
obstinate cases the patient should be required to fast until dinner- 
time. If the drug be not itself a purgative, from four to eight hours 
after its administration a brisk cathartic should be given; or a purga- 
tive dose of calomel may be combined with it, as the bilious purging 
induced by the latter drug seems to be especially obnoxious to 
the entozoa. 

SANTONICA. 

Levant Wormseed consists of the unexpanded flower-heads of Arte- 
misia pauciflora, a composite of Northern Middle Europe and Asia. 
It consists of pale, greenish-brown, smooth heads of four or five 
tubular flowers of a very strong aromatic odor when rubbed, and a 
bitter, disagreeable taste. It contains volatile oil, resinous matter, 
and a crystalline principle, santonin, the anhydride of santoninic acid, 
which occurs in colorless, pearly, four-sided, ortho-rhombic, very 
insoluble tables. It has a neutral reaction, but unites with alkalies 
to form salts, and hence is freely soluble in alkaline solutions. 

639 



640 EXTRANEOUS REMEDIES 

Official Preparations : 

Santoninum 2 to 4 grains (0.i:J-0.26 6m.). 

Trochisci Santonini (each A grain) 2 to 6 troches. 

Physiological Action. — Absorption and Elimination. — Santonin is 
only feebly irritant. It is absorbed readily, probably as a sodium san- 
toninate, and by its elimination produces a very pronounced reddish 
discoloration of the urine, which is characteristic of the poisoning. 

According to the researches of Jaffe, santonin is eliminated as a 
new substance — santogenin, and also as a derivative of santogenin — 
H-oxysantonin. 

The color of the urine is a very marked yellow, which has at first an orange tint, 
but after veiy large doses becomes saffron-like, or sometimes even a purplish red, 
which has given origin to the idea that blood was present in it. According to Manns, 
the addition of an alkali to the yellow urine causes it to become red. 

The exact form in which santonin is thrown off is not established, 
but probably it undergoes oxidation in the system. Kletzinsky 
asserts that the drug receives in the system six atoms of oxygen.* 

Santonin must have a powerful action upon the nervous system, 
but we have no detailed knowledge as to its general physiological 
action. Santonin often increases the flow of urine, and, according 
to Farquharson, it also increases slightly the elimination of urea. 

Therapeutics. — Santonin was introduced into therapeutic use 
in 1830 almost simultaneously by Alms and by Kahler, and is one of 
the most reliable remedies that we have in the treatment of the lum- 
bricoid or round-worm. Von Schroder believes that he has proved 
by direct experiment that santonin is feebly toxic to the round- 
worm; but in this he is in opposition to the general clinical experience 
and the almost universal belief of helminthologists that santonin 
acts directly upon the intestinal parasite. It certainly is a very 
efficient remedy, but it should either be combined with or followed 
in about two or three hours by a brisk cathartic. The combination 
of calomel and santonin has been much commended. 

As long ago as 1862 Guepin and Martin recommended santonin 
in amaurosis, asserting it to be especially useful in those cases in 
which there had been choroiditis and iritis. These statements have 
been confirmed by D. Dyce Brown, as well as by Ogston. G. Frank 
Lydston affirms that santonin is a valuable remedy in epilepsy. D. H. 
Berge3 r asserts that santonin has especial relations with the uterus, 
and, if given in full dose at the time of the molimen, is an efficient 
remedy in acute suppression of the menses. 

Toxicology.- — The first and most characteristic symptom pro- 
duced by large doses of santonin,— xanthopsia, or yellow vision, is 
probably due to a direct action of the poison upon the retina. 

* Chrysophanic acid produces a discoloration of the urine similar to that caused by santonin. 
According to Hoppe-Seyler, the cause of the coloration can readily be distinguished by adding 
sodium hydroxide to the urine, and then shaking up with amyl alcohol, when, if the coloration 
proceeds from santonin, the urine is decolorized, while, if it be due to chrysophanic acid, the alcohol 
takes up only traces of the coloring matter. 



ANTHELMINTICS 64] 

Xanthopsia was firel noticed by Calloud. Usually it consists <>f a very deep 
yellow tint imparted to the landscape and to every object looked at, an clYccf 
perhaps most comparable to that of looking through yellow glass; sometimes this 
yellow is replaced by green; and 1 leydlolT slates that lie has seen patients in whom 
the tint was red, and others in whom it was blue. As was first pointed out, by Knies, 
the period of yellow vision is usually preceded by one of violet vision, and dining 
the stage of yellow vision there is a lessening or complete destruction of the sensi- 
bility towards the violet end of the spectrum. Two theories have been advanced 
as to the cause of the yellow vision; first, (hat if is simply due to staining of the 
humors of the eye, but Rose was unable to find any dyestuff in any portion of the 
body except in the medulla of the kidney; and Filehne, in a very large series of 
studies upon human beings and lower animals was unable to find any staining 
either of the humors or of the retina itself. Moreover, the theory of staining does 
not satisfactorily account for the violet vision which precedes the yellow, nor for 
(he later failure of the power of recognizing violet. The second theory, that the 
disturbance of vision is due to the action of the drug upon the retinal elements 
themselves, would seem to be strengthened by the statement of Filehne that changes 
in the visual purple can be demonstrated in animals fatally poisoned with santonin. 
The accuracy of this statement is, however, denied by Knies, who affirms that 
santonin has no influence upon (lie visual purple or the function of the rods of the 
retina, so that the matter would seem to be still sub judicc. 

lit poisoning by santonin great pallor of surface, with a blue 
color around the eyes or involving the whole countenance, has been 
generally an early symptom; vomiting has not rarely been present, 
and sometimes has been accompanied by colicky pains. Besides 
these manifestations, giddiness, mental apathy or stupor, great 
coldness of the surface, profuse sweating, trembling, mydriasis, and 
finally loss of consciousness, with convulsions, often violent and 
accompanied by opisthotonos and emprosthotonos, and failure of 
respiration, are the usual phenomena of santonin-poisoning. The 
circulation seems to be very little affected.* 

According to Frohner, moderate doses of santonin produce in domestic animals 
polyuria, sometimes strangury, and very commonly so pronounced sexual excite- 
ment as to suggest thai the drug may have value as an aphrodisiac. The toxic 
dose causes in dogs and other domestic animals accelerated breathing, slowing of 
the pulse, universal trembling, cramps, free salivation, unconsciousness, convul- 
sions, dilated pupils, and death. f After death the lesions are not absolutely con- 
stant, but hyperemia of the nerve-centres and congestion of the lungs and heart 
are nearly always present. 

The smallest dose causing fatal poisoning, which we have seen, 
is that reported by Grimm. In this case, a rather feeble child five 
years old took two one-grain doses of santonin, and was seized with 
convulsive tremblings, which increased in severity until they became 
severe convulsions, accompanied by unconsciousness, trismus, pallor 
of the face, cold sweats, dilated pupils, and rapid pulse and respiration. 
Thirteen or fourteen hours after the ingestion of the poison, while 
the patient lay on her back, quiet, unconscious, with moderately 

* Case, Arch, jiir Exper. Path, und Pharm., vi. 302. 

t See experiments of Manns (Das Santonin, Marburg, 1851), of Rose (Virchow's Archil), 1859, 
xvi.), of T. Krauss (Inaug. Diss. Tubingen, 1809), and of Frohner (M onatshefte f. Thierheilk., 
1893. iv.). 

41 



642 EXTRANEOUS REMEDIES 

dilated pupils and a slow, feeble pulse, death occurred suddenly. 
In several other instances doses of from four to six grains have proven 
fatal to children.* 

It is a curious fact that some of the text-books advise the use of 
santonin in doses larger than those which have produced serious or 
even fatal poisoning. Very alarming symptoms have been occasioned 
in a child three and a half years old, by one and one-half grains. 
The reason large doses have been so often given with impunity is the 
great insolubility of the crystals of the drug. 

The treatment of poisoning by santonin, after evacuation of the 
stomach and bowels, must at present be entirely tentative. One 
case appears to have been saved by artificial respiration; but Binz has 
found amyl nitrite, morphine, and artificial respiration alike useless 
in animals; chloral given before the poison appeared to be of service. 

Administration. — Santonin is best administered in troches, 
so that the slow solution of the santonin in the intestine shall produce 
the greatest possible effect upon the worm with the least absorption 
of the remedy. The dose for a child two years old is one-quarter to 
one-half a grain (0.016-0.03 Gm.). For young infants, santonin is 
hardly a safe remedy in any efficient dose. When a dose of any size 
is given, it should not be repeated in less than eight hours, and the 
last dose should be accompanied by a purgative amount of calomel. 

The soluble sodium santoninate is much more dangerous and less 
efficient than santonin: the object is to get as much of the remedy 
as possible in contact with the worm, and, as in order to do this a 
slow, not a rapid, absorption is necessary, the insolubility of santonin 
is an advantage. 

SPIOELIA. 

The rhizome and roots of Spigelia marilandica, or Pinkroot, an 
herbaceous perennial, growing in the Southern and Southwestern 
United States. It consists of a knotty head, with numerous fine, 
crooked, branching rootlets. The odor is faint and peculiar; the 
taste sweetish and slightly bitter. W. L. Dudley separated from it 
an alkaloid, spigeline, which, according to Boorsma, is actively 
poisonous. 

Physiological Action. — Full therapeutic doses of spigelia pro- 
duce in man no symptoms, but, according to Hodge Thompson 
(quoted by Eberle), Eberle, and Spalsberg, an overdose causes acceler- 
ation of the pulse, dilatation of the pupils, heat and dryness of the skin, 
flushing and a swollen appearance of the face, with, in Eberle's cases. 
talkative delirium. Two fatal cases | of poisoning by it are said to 
have been recorded. According to H. A. Hare, toxic doses slow the 
pulse and depress the heart, the respiratory centre, and the motor 
spinal cord. 

* References for these cases: P. J. Tr., viii. 996; ix. 696; B. G. 1 '.. lxxiv. 362; S.Jb.. cci. 128. 
See also W. J. Kilner, St.. Thomas Hosp. Rep., and C. Bevill, n . G., iii. 428; Berg, Wurtemburg. 
Med. Correspondenzbl., i862. 

t These cases appear to have been indefinitely copied, and are of doubtful authenticity. 



\\ rn i:i..\i iNT ies 



643 



In Hare's experiments toxic doses of spigelia caused in the dog hurried respira- 
tory movements, retching, wide dilatation of the pupil, internal strabismus, marked 
exophthalmia, muscular weakness and loss of coordination, and at last sleep, pass- 
ing into coma and death from failure of respiration; in the frog exophthalmia, 
excessive muscular weakness, loss of reflex activity, and slowing of the heart, with 
at lirst increase of power of the systolic contractions but afterwards arrest in a 
condition of semi-diastole. 

Therapeutics. — Spigelia is a most efficient remedy in cases 
of the round-worm, and is, when given within the bounds of modera- 
tion, entirely safe. It appears to narcotize the worm, and requires 
the use of a brisk cathartic. The only preparation official is the 
rluidcxtraet (Fluidextractum Spigeli.e), the dose of which for an 
adult is 2 fluidrachms (8 C.c). It is generally combined with senna. 



OIL OF CHENOPODIUM. 

The Chenopodium anthelminticum, or Jerusalem Oak, is a rank, 
odorous plant, growing about waste places in the suburbs of towns 
in the United States. The seeds (sometimes known as American 
wormseed) are minute, globular, are light brown and about the size 
of a pin's head, of a nauseous odor and a pungent taste, due to the 
volatile oil which they contain in large quantity. 

The oil of chenopodium, the only derivative of the plant official 
(Oleum Chenopodii), is of a light yellow color, becoming darker and 
less fluid by age, of a peculiar powerful odor and a hot burning taste.* 

According to Briinning the oil of chenopodium produces, in both 
frogs and rabbits, paralysis through depression of the spinal cord; 
and in the mammals, paralysis and respiratory failure. Added to 
blood outside the body it causes methemoglobin. Briinning also 
finds that in proportions of one part to two hundred it has a distinct 
antiseptic action; while 1 to 5000 narcotizes but does not kill the 
Ascarus mystax (round-worm of dogs). It has been used in hysteria, 
but is now employed only as an anthelmintic against the lumbricus, 
and more rarely the tapeworm. It is very efficient, and ten minims 
(0.6 C.c.) of it, on sugar, may be given to a child three years old, 
before breakfast, dinner, and supper, for two days, followed by a 
brisk purge. 

ASPIDIUM. 

FUix-Mas, or Male Fern, is the rhizome of Dryopteris Filix-mas, 
or male fern of Europe. Under the name of Aspidium f the present 
U. S. Pharmacopoeia reccgnizes both it and the rhizome of the indige- 



* In the Maryland Med. Journ 
uted to the taking of an ounce or m 
in bed unconscious, with vomited m; 
relapsed an hour or two later into h 
aphasic, deaf to conversation, acute 
apoplexy. It is improbable that th< 

t It is probable that many specif 
Path. u. Pharm., 1895, xxxv.) separat 
allied to filicic acid, a yellow and a 
found these extracts of the plant to 



iv. CO, T. R. Brown reports a case in which death was attrib- 
>re of wormseed oil in divided doses. The patient was found 
tters over his surroundings, after some hours became sensible, 
avy sleep, was again roused, and while playing cards became 
y sensitive to other sounds and finally died of hemiplegic 
wormseed was the direct immediate cause of the fatal result. 

of the genus Aspidium are active. Poulsson (Arch. J. Exper. 

1 from the rhizome of Aspidium spinulosum two acids closely 

hite polyslichic acid; and both he and Valter Laurtfn have 

>e active tajniacides. 



(ill EXTRANEOUS REMEDIES 

nous D. marginal!*. The rhizome, when perfect, is from six to twelve 
inches long, and covered with large, brown, imbricated scales. Its 
taste is bitter and astringent. 

The official oleoresin (Oleobesina Aspidii) thoroughly repre- 
sents the crude drug. It is a dark, thick liquid, of a bitter, nauseous, 
slightly acrid taste. 

Aspidium contains an amorphous acid, filieic * which, according to the experi- 
ments of E. Poulsson, is a very active substance, causing, in the frog, at first 
excitement and then paralysis of the central nervous system, and finally paralyzing 
the heart and exerting a marked influence upon the muscles: producing in warm- 
blooded animals violent diarrhoea, with a general paralysis due to depression of the 
spinal centres, and finally cardiac palsy. Robert, however, as the result of his 
experiments, believes that the vermifuge principles of male fern do not depend 
solely or even chiefly upon filieic acid, but upon the ethereal oil. 

In overdose it is a violent poison, producing excessive vomiting 
and purging, with general weakness, tremors, cramps in the extremi- 
ties, increased reflexes, amaurosis, and finally, in some cases, violent 
tetanic convulsions, with opisthotonos, stupor deepening into coma, 
and collapse. Icterus is sometimes apparent. Disturbance of the 
special senses is a not infrequent symptom in aspidium-poisoning. 
Deafness without loss of vision has been noted (case of Grant). .More 
commonly amblyopia or complete amaurosis occurs. One or both 
eyes may be affected, and total blindness, with gray atrophy, may 
remain as a permanent condition (Katayama and Okamoto; also 
Bayer). Experiments upon dogs indicate that the primary influence 
of the drug is on the ganglion-cells of the retina. 

The icterus of aspidium poison has been attributed to the inflammation of the 
duodenum, but Grawitz, conceiving that it might be of hemic origin, found on 
examination of the blood of patients that immediately after the taking of large doses 
of the extract of male fern there was a marked lessening in the number of the red 
blood-corpuscles. Grawitz, therefore, came to the conclusion that the extract is 
powerfully destructive to the red blood-disks, and that the icterus was hemic in its 
etiology. C. Georgiewsky has found that in rabbits, fatally poisoned with male 
fern, no destruction of the red blood-corpuscles occurs if death takes place within 
twenty-four hours; but that if the symptoms be protracted over several days there 
is a very distinct lessening in the amount of hemoglobin in the blood; and tliat 
after death the characteristic change of the poisoning is a pronounced wide-spread 
deposit of ferrous pigments in the liver, the spleen, the marrow of the bones, and 
sometimes in the kidneys. In these later researches, the theory of Grawitz that 
the poison acts specially upon the liver-cells was not confirmed. 

After fatal poisoning in the lower animals by aspidium, besides 
the granular pigmentation just spoken of, hemorrhagic gastro-enteritis 
and cystitis, with violent parenchymatous nephritis, may be found 
(Frohner). The fatal result is partially due to violent irritation of 
the gastro-intestinal tract of the kidneys; but Quirll is probably 
correct in his belief that it is also largely the outcome of the influence 

* Asvidin of R. Boehm (Arcliiv f. Exper. Path. u. Pharm., 1S9G, xxxviii.) is distinct from 
fiiicic acid, and although poisonous both to frogs and to higher animals, appears not to be an active 
tujniacide. 



WTHKhMINTlCS 



oir> 



of the poison upon the nerve-centres, to which factor should also 
In- added its action upon the circulation. The minimum fatal dose 
of the oleoresin is hardly known, hut- eight grammes of the extract 
have caused death in a child about three years old; six drachms of 
the oleoresin have several times proved fatal in the adult: * in Pal- 
tauf's case the fatal result is said to have been due to four and a half 
grammes. 

Therapeutics. — Male fern is employed almost exclusively 
against the tapeworm. In its administration it is necessary to regard 
strictly the general rules applying with greater or less force to all 
anthelmintics, but which are especially imperative when a drug is 
employed against the tapeworm. The patient should live upon milk 
and a little bread for one day, and the following morning take a full 
dose — one-half to one fluidrachm (2-4 C.c.) — of the oleoresin, fast- 
ing, and repeating it in two or three hours. At noon the patient 
may eat freely, and in the evening a brisk cathartic should be given. 

Pepo. — Pumpkin Seed. — The seeds of the ordinary pumpkin, 
Cucurbit a pepo, are a valuable remedy in cases of tapeworm, perhaps 
even more efficient than the male fern, and perfectly harmless. Two 
ounces (62 Gm.) of the seeds may be beaten up with sugar into an 
electuary, or with water into an emulsion, and be taken fasting in 
the morning, the patient having dieted the previous day. Some 
hours after their administration a brisk purge should be given. T. (i. 
Wolff asserts that the active principle is a resin, which he has found 
efficient in doses of fifteen grains (1 Gm.). 

Kousso (Cusso), Brayera, is the female inflorescence of Hagenia 
abyssinica, a tree of Abyssinia. It occurs in compressed greenish- 
yellow clusters, of a fragrant balsamic odor, and a taste which in a 
little while becomes acrid and disagreeable. 

The crystalline resin kosin, discovered by Pavesi, is believed by Bedall to be 
the active principle of kousso. Leichsenring affirms it to be kosotoxin, an amor- 
phous, yellowish-white substance, which, according to Handmann, is an active 
paralyzant to all muscles, including the heart, and also of the motor nerve-endings. 

Brayera is a most efficient remedy against the tapeworm, and even 
in large doses causes no greater inconvenience to the patient than 
some nausea, abdominal pain, and looseness of the bowels. It is 
generally not necessary to administer any purgative with it, and the 
worm is discharged dead with the last watery passages. A half-ounce 
of the powdered flowers is given suspended in water in the morning, 
with the usual precautions as to diet. The best preparation is the 
yellowish-brown, impure, amorphous kosin of commerce, which may 
be given in doses of seven to fifteen grains (0.5-1 Gm.) repeated 
every half-hour until four doses have been taken, a full dose of castor 



* Therap. Monatsch., 1889, iii.; Miinclten Med. Wochen., 1890, xxxvii.j Lancet, 1882; 
Mtd. Wuchen., 1891, xvii. 



Deutsch. 



646 EXTRANEOUS REMEDIES 

oil being administered one hour later. Care should be exercised 
in giving brayera to pregnant women, as it is stated that it has 
produced abortion. 

Pomegranate Rind. — The bark of the stem and root of the pome- 
granate (I'unica granatum), although very unpalatable, is efficient 
against the tapeworm. As originally stated by C. Tanret, pomegranate 
bark contains four alkaloids; the most important are pelletierine 
(punwine) and iso-pelletierine (iso-punicine) . The official pelletierine 
tannate is a mixture of the four alkaloids. 

Official Preparations : 

Fluidextractum Granati 30 minims (2 C.c). 

Pellet ierinae Tannas 4 grains (0.25 Gm.). 

In the higher animals these alkaloids paralyze the peripheral 
motor nerves, having a curare-like action, without affecting sensation 
or muscular contractility. G. Coronedi agrees with the statement 
that the paralysis is peripheral, but believes that the muscles them- 
selves are affected. The efficiency of pelletierine as an anthelmintic 
has been shown by Dujardin-Beaumetz and confirmed by various 
clinicians. Dujardin-Beaumetz also has employed it successfully in 
Meniere's disease, and states that hypodermic injections of six grains 
(0.4 Gm.) produce in man severe vertigo and muscular weakness, 
with great retinal congestion. We have seen five grains cause in the 
adult pronounced muscular weakness amounting almost to general 
paralysis, and a number of cases have been reported in which it has 
produced in infants symptoms so severe as to discourage its employ- 
ment in patients of that class.* Galezowski has used pelletierine 
in paralysis of the third and sixth pairs of nerves with asserted 
good results. 

Thymol has been used by Neuma Campi f for the destruction 
of tapeworm; he gives half an ounce of castor oil in the evening, in 
the morning two drachms (7 Gm.) of thymol divided into twelve 
doses, one to be taken every quarter of an hour, and twenty minutes 
after the last dose of thymol another dose of castor oil. Thymol is 
a specific against hook-worms — the Ankylostoma ( Uncinaria) duodenale 
and the A. (U.) Americana. After starvation for twenty-four hours, 
a thirty-grain dose may be given and repeated in twenty-four hours, 
followed by a brisk purge, as suggested by F. M. Sandwith. Giddi- 
ness, fall of temperature from 1° to 2° C., slowness of the pulse and 
respiration, staggering, and even collapse are liable to occur; a cure 
is almost invariably effected by such doses, but probably smaller 
amounts would suffice. 

Om op Turpentine, in doses of half a fluidounce, has been used in cases both 
of tapeworm and of round-worm. It is efficient, but is liable to produce unpleasant 

* See Bull, de Therap., lxxviii., lxxx., cxi., July, 188G; also University Med. Magazine, i. G39. 
1 11 Raccoglitore Medico, abstracted in Buffalo Med. Journ., Oct. 1886. 






ANTHELMINTICS 



647 



effects, and should be employed only when other remedies have been used without 
success or are not to be had. It should lie given in combination with twice its bulk 
of castor oil, or sometimes in smaller doses as an aid to other vermifuges. 

Kamala. — Kamala. — The glands and hairs from the capsules of Mallotus 

Philippinensis are used against the tapeworm. It is an orange-red, very inflammable, 
granular powder, mixing with water with some difficulty, and containing traces of 
a volatile oil and coloring resinoids, to one of which Anderson has given the name of 
rottlerin. Kamala is actively purgative, indeed drastic, and may cause nausea and 
vomiting. A tincture of it may be used. Dose of the powder, one to two drachms 
( I s ton.) in syrup, given in the morning: repeat in ten hours if it does not purge. 

A/.koakach, the bark of the root of Melia azedarach, or Pride of China, is used 
in the South as a, remedy for the round-worm. It is said to possess poisonous proper- 
ties similar to those of spigelia, yet it is affirmed that animals and children eat its 
fruit with impunity. It is usually given in decoction (two ounces to one and a half 
pints, boiled to a pint), the dose being for a child a tablespoonful (15 C.c.) every 
two or three hours until the bowels are affected. 

Acidum Picrum. — Picric or carbazotic acid, on account of its corrosive char- 
acter, is used internally exclusively in the form of the ammonium picrate, which, 
according to Erb, is rapidly absorbed and eliminated in the urine, and produces, 
in doses of fifteen grains, yellowness of the conjunctiva, skin and urine, often 
accompanied by gastric disturbances. Von Beck reports urticaria and measles-iike 
eruptions produced by the long use of the drug; and Achard and Clerc have seen 
violent general erythematous swelling of the limbs produced by the local application 
of the solution of yicric acid. 

According to Binz, picric acid acts similarly to but much less powerfully than 
does quinine upon infusoria. W. Erb found that a single dose of eight grains will 
produce in the rabbit falling temperature, weakness, diarrhoea, collapse ending 
in death, sometimes preceded by convulsions. The blood of animals slowly killed 
by the picrate was a dirty-brown color, with distinct nuclei in the red blood-disks 
and floating free in the serum. The alterations in the red blood-corpuscles occurred 
during life, and could be produced by mixing ammonium picrate with blood outside 
of the body. Ammonium -picrate has been commended as an antiperiodic, but 
is of no value; nor does it seem useful as an anthelmintic or in trichiniasis. (See 
Erb.) Hammond declares that the salts of picric acid are specific in exophthalmic 
goitre. According to Erb, the ammonia salt, nine to twelve grains a day, may 
be given with safety. 

REFERENCES. 



Achard and Clerc. .G. H. M. C, 1900, xlvii. Grimm. 

Bayer Prag. Med. Wochens., 1888, 

xii. 
Bedall Syd. Soc. Year-Book, 180S, 

470. 

Bergy Araer. Therap., Julv, 1892. 

Binz A. E. P. P., vi., 300. 

Binz V. A. P. A., xlvi. 130. 

Boorsma P. J. Tr., 1898. 

Brown Brit, and For. Med.-Oliir. 

Rev., 1872. 

Brinnin.. Z. E. P. T., 1905, i. 80. 

Ooronkdi La Sperimentale, 1892. 

Kheri.e Materia Medica and Thera- Paltauf 

peutics, i. Poulsson 

Erb Die Pikrinsaure, Wurzbunj;, Rose 

1805. 
Farqdh u(son. . . . B. M. J., 1872. 

I'n.iHNK A. G. P., 1900, lxxx. Sandwith 

Fhohner Monats. Prakt. Thierheilk., Spalsberci. . . . 

1890. Tanret 

Galezowski B. M. J., Nov. 28, 1885. Von Beck 

Qb kNT S. .lb., ccxlix. Von Schroder 



Guepin and M 

Hammond 

Hare 

Jaffe 

Kataya.ma and 



Knies. . . 

KOBERT. 

Manns. . 



Schweizer Zeitsoh. f. Med. 

Chir., u. Geb., 1852, 493. 
ARTiN..Ann. de Therap., 1862. 
. .N. Y. M. J., Jan., 1890. 
. .M. News, March 12, 1887. 

P. J. Tr., 1897, lix. 
Okomoto .. . Viertelj. f. Ge- 

richt. Med. u. Off. San., 

1894, viii. Suppl. 
. .A. of Op., 1900, xxix. 
. .Th. M., 1893. 
. . Das Santonin, Marburg, 

1851. 
. S. Jb., cexxxvi. 
. . A. E. P. P., 1891, xxix. 
. . V. A. P. A., xvi. 233; xviii. 

15; xLx. 522; xx. 245; 

xxviii. 30. 
. . Anchylostomiasis, 1894. 
. .B. M. S. J., 1885. 
. ,B. G. T., xcviii. 31G. 
. . Charite-Annalen, 1892, xvii. 
. . A. E. P. P., xix. 304. 



FAMILY III.— DIGESTANTS. 



In this family are associated a few remedies which are used to 
aid the alimentary canal in dissolving the various articles of food. 

PEPSIN. 

As is well known, there is secreted by the gastric glands a peculiar 
albuminous body, which has the power of dissolving, when in acid 
solution, coagulated and insoluble proteids.* To this principle the 
name of pepsin has long been given. A discussion of its nature and 
properties would be more in place in a work on physiology than 
in one on therapeutics. Pepsin is required by the U. S. Pharma- 
copoeia to be able to digest three thousand times its weight of freshly 
coagulated egg albumin. 

Various processes have been suggested for the preparation of the 
drug, but none of them yields a pure proximate principle, if indeed 
pepsin have really such nature and be not an albuminous body of 
varying constitution. 

The activity of pepsin is destroyed by a large number of substances. 
Among its known incompatibilities the most important from the 
standpoint of the practical prescriber are: Alcohol, alkalies, strong 
acids (more than one-half per cent, of hydrochloric acid), various 
metallic salts and tannic acid. Consequently we think the physi- 
cian should eschew all elixirs or compound preparations of the 
drug, using only the powdered pepsin or a glycerite of pepsin, 
or a freshly prepared solution in water containing 0.2 per cent, of 
hydrochloric acid. If other remedies are to be given it is no great 
hardship to write a second prescription for them. 

Therapeutics. — The value of pepsin in practical medicine is 
very questionable. It is very rarely lacking in the ordinary forms of 
gastritis or dyspepsia, the inactivity of the gastric juices in these 
cases being due to the absence of hj'drochloric acid. Moreover, the 
doses in which it has been given and the methods of its exhibition 
have generally been such as to make it certain that any beneficial 
effects following its administration were due to some other cause 
than the pepsin. 

The value of pepsin has been overestimated, and it has been given 
to adults in ridiculously small doses: at least half a drachm (2 Gm.) 
of the ordinary commercial article should be exhibited at a dose. 

* The milk-curdling ferment of gastric juice and of rennet is not pepsin. 
648 



DIGESTANTS 649 

PANCREATIN. 

Pancreatin has boon used to considerable extent as a digestanl 
and is recognized by the V. S. Pharmacopoeia. It is highly improb- 
able, however, that it can exercise any beneficial influence upon the 
digestive processes, as Sollmann lias shown that a mixture of one- 
tenth per cent, hydrochloric acid and pepsin completely destroys 
its digestive properties. Of the numerous concoctions which are 
largely exploited by their proprietors, and professed to contain both 
pancreatin and pepsin, it seems hardly necessary to speak were it 
not for the fact that they are so widely employed in medicine. It is 
absolutely impossible that they can contain both of those active fer- 
ments, and it is probable that they contain neither. Pancreatin, how- 
ever, has a place in medicine for the preparation of predigested foods. 

It must be remembered that most peptones have a distinctly 
bitter taste and therefore thoroughly digested foods are very unpal- 
atable. The bitterness may be partly concealed by the addition of 
aromatic flavoring extracts, but more commonly it is the custom 
to arrest the process of digestion before it is complete. 

At first thought pepsin would appear to be the most available ferment for the 
preparation of peptones; but practical experience has led to reliance upon pan- 
creatin. Pancreatin, pancreatic extracts, and pancreatic liquors are now found 
abundantly in commerce. The superiority of the secretion of the pancreatic gland 
as a practical ferment is connected with the fact that- it contains two distinct classes 
of digestive principles, — namely, pancreatic diastase, which dissolves starch, and 
trypsin, which acts upon albuminous principles. It is of great importance to be 
able to determine readily the value of any preparation of pancreatin. The test 
devised by William Roberts (Digestive Ferments, London, 1881) appears to be very 
practical. If pancreatin be added to fresh milk without an alkali, in the course of 
a few minutes the liquid acquires the property of curdling abundantly upon boiling; 
and Roberts estimates the value of a pancreatin by the number of cubic centimetres 
of milk which are transformed by one cubic centimetre of the sample at a temper- 
ature of 40° C. to the curdling point in five minutes. A test which may be substi- 
tuted for that of Roberts, and which is especially applicable to the ordinary pan- 
creatic extracts or so-called pancreatin, is based upon the peptonizing power of the 
powder. Five grains of it added to twenty grains of sodium bicarbonate should so 
alter the casein contained in one pint of milk at a temperature of 115° F. in an hour, 
that no coagulation will occur upon the addition of nitric acid. 

To make peptonized milk add 5 grains of pancreatin and 20 grains 
of sodium bicarbonate to a pint of milk, at a temperature of about 
100° F. Digestion will be complete in one hour or one hour and a 
half. If the bitter taste which is developed is seriously objected to, 
the digestive action may be stopped at the end of a half hour by 
heating the milk almost to the boiling point. 

To make peptonized gruel prepare a thick gruel with arrow root, 
oat meal or other farinaceous article, add while still heated an equal 
quantity of milk and when cooled to about 100° F. 5 grains of pan- 
creatin and 20 grains of sodium bicarbonate to each pint of the 
mixture. Digest at blood heat for two hours. Raise to boiling point 
and then strain. 



650 EXTRANEOUS REMEDIES 

To make peptonized beef tea, simmer half a pound of minced beef 
for two hours in a pint of water containing twenty grains of sodium 
bicarbonate, allow to cool to about 100° F., digest at this tempera- 
ture with a tablespoonful of liquor pancreaticus or ten grains of 
pancreatic extract for three hours, decant and momentarily boil. 
This beef tea is said to be about equivalent to milk in nutritive 
value, containing 4.5 per cent, of organic solids, three-fourths of 
which is peptone. 

MALT. 

Malt is the seeds of ordinary barley caused to enter the incipient 
stage of germination by artificial means and dried. It is prepared 
by soaking the grains in water and leaving them in heaps in a room 
of moderate temperature, and by occasional turning preventing the 
heat given off during the process of germination from accumulating; 
then finally killing the germ with heat. The color varies from pale 
amber to black, according to the degree of the heat used in drying. 
There is formed during germination a peculiar ferment, diastase, 
which is able to convert starch into dextrin and glucose. The 
Extractum Malti of the IT. S. Pharmacopoeia is made by rapidly 
evaporating an infusion of malt to the consistency of a thick, honey- 
like liquid at a temperature not above 130° F. It should contain 
practically all the diastase of the malt. The odor of the extract of 
malt is slight and peculiar, the taste sweet, and the reaction to paper 
distinctly acid. It dissolves freely in water, and is precipitated by 
alcohol, tannic acid, mercuric chloride, and various other metallic 
salts. Commercial malt extracts vary greatly: some of them are 
practically preparations of glucose, others are of the nature of strong 
or weak beers; true extract of malt contains no alcohol at all. 
There are also on the market a number of more or less pure 
preparations of diastase; the better of these are much more eligible 
preparations. 

Therapeutics. — R. H. Chittenden and G. W. Cummins have 
found that diastase acts better in a neutral than in an alkaline solu- 
tion; that proteid matters when present in the alkaline solution 
prevent the retarding influence of an alkaline carbonate; that neutral 
peptone exerts a direct stimulant effect on the amylolytic action, 
but that the greatest amylolytic action is observed in the presence 
of proteid matter partially saturated with acid, although a larger 
percentage of acid-proteids may cause complete destruction of the 
ferment. These results seem to prove that diastase, when taken 
into the stomach, must sooner or later be completely destroyed by 
the gastric juice, and that in order for it to have any distinct effect 
upon digestion it must be given at the beginning of the meal. In 
cancer of the stomach and other diseases in which the gastric juices 
lack acidity, the action of diastase upon starch must be more pro- 
nounced; but unfortunately the failure of the starch-digestion is 
usually associated with gastric hyperacidity. 



DIGESTANTS 651 

Patain. The Oarica Papaya is an herbaceous tree universally cultivated in 
tropica] countries for its fruit, t ho papaw, the juice of which yields a peculiar fer- 
ment, to which the name of /«i/»i/'« was given by Wurtz; it is now also known by 
the name originated by Pokolt, papayotin. This substance is a ferment, which has 
the power of dissolving fibrin, muscular fibres, tissues, etc. Its action on albumi- 
noids is said to resemble that of trypsin rather than that of pepsin. (See Martin.) 

Papain has been used in medicine as a substitute for pepsin, in doses of five to 
ten grains (0.3 -0.6 Gm.)< It has also been very highly recommended for the purpose 
of destroying organic tissues of low type, as in diphtheria (A. Jacobi), in the thicken- 
ing of chronic eatema, in warts, and in pyogenic membranes surrounding old sinuses 
or abscesses. It is not caustic, but simply dissolves the diseased tissues, and is said 
to cause no pain.* It should be applied, one part each of papain, glycerin, and 
water. In our laboratory experiments commercial papain of the most esteemed 
brands has failed to exert any solvent power over albuminous substances, and it is 
probably a remedy of little value. 



REFERENCES. 

DIGESTANTS. Si ..i.mann J. A. M. A Feb. 2, 1907. 

Jacobi T. G., ii. Martin B. M. J., Ju'v 25, 1885. 



* Birmingham Med. Rev., May, 1880. 



FAMILY IV.— ABSORBENTS. 



This class contains remedies which are used for the purpose of 
absorbing acrid and deleterious materials, such as offensive discharges 
on the exterior of the body, and acrid secretions, or the irritant prod- 
ucts of the partial decomposition of food, in the alimentary canal. 
For the first purpose very fine dry earth and plaster of Paris are used 
to some extent in practice; but, as their employment is purely within 
the province of the surgeon, we shall say no more about them here. 

CHARCOAL. 

Charcoal is official in the U. S. Pharmacopoeia in two forms: 

Carbo Ltgni. — Charcoal prepared from wood. 

Carbo Animals. — Animal Charcoal, prepared from bone. 

Charcoal for medicinal purposes should be made out of a light, 
porous wood: that prepared from the young shoots of the willow or 
of the poplar is almost exclusively employed. It is a black, brittle 
substance, and should have more or less lustre. It has a very 
remarkable power of absorbing many times its own bulk of gases, 
and, when exposed to the air, increases rapidly in weight. It 
should, therefore, when intended for medicinal purposes, be pow- 
dered as soon as it is burnt, and put in small, completely-filled, 
closely-sealed bottles. 

Animal charcoal, or bone-black, formed as it is by the partial 
burning of bones, contains a large percentage of calcium phos- 
phate and carbonate. Purified Animal Charcoal (Carbo Animalis 
Purificatus) is prepared by removing the lime salts by dilute 
muriatic acid. 

Therapeutics. — Internally, charcoal is employed as an absorb- 
ent in fermentative intestinal dyspepsia, cardialgia, and similar 
disorders. As moist charcoal is not an absorbent, it is evident that it 
is of very little value; its habitual employment is generally combined 
with that of laxatives for fear of accumulation in the alimentary 
canal. Dose of charcoal, from one to two drachms (4-8 Gm.). Except 
in a mechanical way, it is perfectly innocuous in any dose. 



652 



FAMILY V.— DISINFECTANTS. 



Disinfectants are agents which are used for the purpose of 
preventing the growth of bacteria. This may be accomplished in 
two ways, — either by killing the germs (germicides) or by rendering 
the media unfavorable for the growth of the micro-organisms (anti- 
septics). All chemical germicides become, however, when in dilute 
solution, antiseptic, so that the natural division of these agents, as 
given above, does not serve well as a basis of a classification for 
systematic study. Disinfectants may be conveniently divided into 
forces, and material chemical groups as follows: 
I. Force*; heat and cold. 

11. Metallic salts, including certain salts of mercury, silver, 
copper, zinc, and iron. 

III. Halogens, including chlorine and the hypochlorites, iodine, 
bromine, fluorine and their various compounds. 

IV. Oxidizing disinfectants, including especially hydrogen dioxide 
and potassium permanganate. 

V. Carbon compounds, including phenol, cresylic acid, creosote, 
salicylic acid, benzoic acid, thymol, menthol, alcohol, formaldehyde, 
the volatile oils and allied drugs. 

VI. Sulphur and Boron derivatives, including especially sul- 
phurous acid, boric acid, and their salts. 

I.— COLD AND HEAT. 

Cold. — The effect of low temperature in preventing the growth of 
micro-organisms is well known and daily taken advantage of by the 
housewife in the preservation of foodstuffs. Very few bacteria will 
multiply at a temperature lower than 40° F. On the other hand, 
cold cannot be considered as a germicidal agent, for it has been shown 
that even the extraordinarily low t'emperature of liquid air does not 
destroy the vitality of the typhoid bacillus and other test organisms. 

Heat. — As a germicide fire is absolutely efficient, but destructive. 
The lower degrees of heat have been used without moisture (dry heat), 
and with moisture (moist heat). 

Moist heat is much more efficient than is dry heat. 

According to Sternberg, while most micro-organisms are destroyed in the pres- 
ence of moisture by a temperature of 62° C. (143° F.), certain of the more resistant 
species of bacteria will withstand a heat considerably higher than this; but all 
bacteria free from spores are destroyed by the heat of boiling water in one to two 
minutes. On the other hand, some spores arc able to withstand boiling water for 
several hours. To destroy with certainty all forms of life requires, according to 

653 



EXTRANEOUS REMEDIES 

Sternberg, an exposure to moist heat of a temperature of 115° C. (239° F.) for half 
an hour. This temperature can of course be produced only under pressure. The 
most satisfactory manner of using this method of sterilization is by means of the 
autoclave, an apparatus so arranged as to prevent the escape of the steam until the 
pressure within the autoclave has reached nine to ten pounds, at which time the 
temperature will approximate 115° C. 

Dry heat is much inferior in its germicidal effect to moist heat. 

Wolf found that dry air at 140° C. was scarcely more destructive than is watery 
vapor at 100°; Koch, that five minutes' exposure to steam was equal to an hour 
or an hour and a half with the dried air. The results reached by Koch and Wolff- 
hiigel are in accord with other evidence, and may be considered correct. They 
are as follows: 

1. A temperature of 100° C. (212° F.), dry heat, maintained for one hour and 
a half, will destroy bacteria which do not contain spores. 

2. Spores of mould-fungi require for their destruction in hot dry air a tem- 
ixrature of from 110° to 11.5° C. (230°-239° F.) maintained for one hour and a half. 

3. Bacillus-spores require for their destruction in hot air a temperature of 
H0°C. (284° F.) maintained for three hours. 

4. In dry air the heat penetrates objects so slowly that packages, such as pillows 
or small bundles of clothing, are not disinfected after an exposure of from three to 
four hours to a temperature of 140° C. (284° F.). 

5. Exposure to a temperature of 140° C. (284° F.) in dry air for a period of 
three hours injures most objects requiring disinfection (clothing, bedding, etc.) to 
a greater or less degree. 

George H. Rohe found that rolls of blankets exposed in a chamber heated to 
2S0° F. for three hours were very slightly affected in their interior. This is in strict 
accord with the teaching of Parsons and Klein, of the London Local Governing 
Board, and of other observers. 

Dry heat is so inferior to moist heat that it is at present never 
employed as a germicide. Quarantine and other health stations are 
or ought to be supplied with apparatus for exposing infected articles 
to the prolonged action of hot steam in chambers, etc. For ordinary 
household purpose, however, the physician is forced to rely upon 
boiling, which, when maintained for thirty minutes, may be considered 
as practically efficient. 

II.— METALLIC SALTS. 

Mercury. — All of the salts of mercury appear to have more or 
less germk ':' properties. The most powerful of them are the 
bichloride a:: .he biniodide. The bichloride of mercury has long 
been recogni;-^ as one of the most powerful germicides known. 

In 1870 John Dougall announced that corrosive sublimate, 1 part in 6500, would 
kill spermatozoa, and 1 part in 6000 infusoria; the later researches of Koch, Jalan 
de la Croix, and Sternberg have confirmed this result, and shown that corrosive 
sublimate is one of the most powerful of known germicides. Micrococci and bacilli 
in active growth without spores are killed by solutions of 1 in 20,000, while solutions 
of 1 in 1000 will rapidly destroy the spores of B. anthracis and B. subtilis. Results 
contrary to these have, it is true, been obtained by Klein, of London, who asserts 
\ iat a one-per-cent. solution of the mercuric chloride is no more a germicide than 
-'h-iporgr; but the evidence to the contrary is so strong that it seems almost a cer- 
t. v .:at there was some error in Klein's experiment. According to the detailed 



^ 



DISINFECTANTS 655 

experiment of Koch, the spores <>f IV anthracis are absolutely incapable of germi- 
nating in ;'. proteid solution if as little as I part of corrosive sublimate in 300,000 I"' 
present, Sternberg has confirmed the experiments of Koch. 

It must be remembered that corrosive sublimate is so readily decomposed by 

ammonia and other substances usually present in a mass of 61th that, it, is not avail- 
able lor disinfectant purposes on a targe scale; even when the amount of organic 
matter is small, the usefulness of corrosive sublimate is often destroyed by its chem- 
ical instability: thus, it should not be employed for the destruction of germs in 
fecal discharges. A standard solution of 1 part in 1000 may be used for bedding, 
which can be soaked in it, for washing the lloors and walls of infected apartments, 
and for disinfecting the hands of surgeons and gynecologists. After the corrosive 
sublimate has done its work it should be removed by fiee washing with pure 
water, liven in the cases just spoken of corrosive sublimate is often inferior to 
formaldehyde. 

For various surgical purposes the sublimate may be used in 
.strength;; varying from 1:2000 to 1:10,000. It is well to add to the 
solutions of corrosive sublimate an equal quantity of ammonium 
chloride or else a small proportion of tartaric or hydrochloric acid, 
as these substances lessen the liability to precipitation. 

The bin iodide of mercury (hydrargyri iodidum rubrum), although 
not nearly so widely employed as the bichloride, seems to be even 
more active as a germicide. According to the experiments of Burgess, 
a 1 : 5000 solution of the biniodide is equivalent in strength to a 1 : 2000 
solution of the bichloride. Sternberg has found that a 1:20,000 solu- 
tion of the biniodide is equivalent to 1 : 15,000 solution of the bichloride 
of mercury. 

The probable reason why the mercuric iodide has not come into 
use as a germicide is the fact that it is almost insoluble in water. It 
may be readily dissolved, however, by the addition of potassium 
iodide or lithium iodide to the solution. Rosenberger and England 
suggest the double lithium mercuric iodide, which is freely soluble in 
water, is not precipitated by the fixed alkalies, and according to their 
experiments is actively germicidal. 

Silver. — The salts of silver rank next to the salts of mercury 
as the most powerful germicides we possess. According to Miquel, 
silver nitrate * prevents the growth of atmospheric germs when present 
in the proportion of 1 part to 12,500. According to Boer, a 1:4000 
solution destroys typhoid bacillus in two hours, but it required a 
1 : 2500 solution to kill the diphtheria bacillus in the same time. Beh- 
ring found that a 1 :10,000 solution is capable of destroying the anthrax 
spores in forty-eight hours. 

Unfortunately, the silver nitrate is an extremely unstable salt, 
being decomposed by the alkalies, the mineral acids, albumin, and 
even decomposing in the air on exposure. 

Various other less active metallic salts have been used in the past 
as disinfectants but are of very little practical value, and have been 
superseded by the numerous active modern germicides. Many of 



For consideration of various non-official preparations of silver see p. 319. 



6o6 EXTRANEOUS REMEDIES 

these salts act chiefly by the capability which they have of taking 
sulphur away from sulphuretted gases, and thereby lessening odor; 
so that they are rather deodorants than disinfectants. The most 
used of these disinfectants are the zinc sulphate, zinc chloride, and 
lead nitrate, the latter forming the basis of the so-called Ledoyen's 
Disinfectant Solution. They should, all of them, be totally disregarded. 
Old iron, and the impure ferrous sulphate (Copperas), have to some 
extent resisted modern innovation, and have been believed to have 
the power of oxidizing organic matter and of attacking disease germs, 
which makes them of value. Of the two, copperas is certainly the 
more efficacious; but in an official study Dr. A. J. McLaughlin has 
shown that it has no dominant influence over putrefactive changes 
unless present to the extent of five per cent. — that its saturated solu- 
tion does not affect pathogenetic organisms, and that the same solu- 
tion mixed with half its bulk of feces fails to disinfect the mass after 
three days. 

III.— HALOGENS. 

CHLORINE. 

Chlorine is a yellow gas, extremely irritant to all mucous mem- 
branes with which it may come in contact. Its solution in water 
(Liquor Chlori Compositus) is recognized by the pharmacopoeia. 
More commonly it is generated extemporaneously when required, 
by the decomposition of a hypochlorite. Two of these are official. 

Official Preparations : 

Calx Chlorinata [Bleaching Powder] Not used internally. 

Liquor Sodse Chlorinata [Labarraque's 

Solution] i to 2 fluidrachms (2-8 C.c). 

Liquor Chlori Compositus 4 to 2 fluidrachms (2-8 C.c). 

Chlorinated Lime or Bleaching-powder (often incorrectly called 
chloride of lime) is a grayish-white substance occurring in powder 
or friable lumps, having a hot, acrid, astringent taste, and an odor 
resembling that of chlorine. It is made by the action of chlorine upon 
calcium hydrate, or slaked lime, and should contain at least thirty 
per cent, of available chlorine. It probably varies in its chemical 
constitution, but, according to the most recent views, is chiefly 
composed of the calcium hypochlorite and chloride. When exposed 
to the air it slowly evolves hypochlorous acid, which, being an 
unstable compound, undergoes spontaneous decomposition, and finally 
sets free fourteen-fifteenths of its chlorine. When an acid is added 
to chlorinated lime, the chlorine gas is rapidly evolved. If a speci- 
men of bleaching-powder be very moist, it generally contains an over- 
proportion of the deliquescent calcium chloride, is correspondingly 
unable to liberate chlorine and is therefore of inferior value. 

Solution of Chlorinated Soda, Labarraque's Solution, is made 
by triturating chlorinated lime with a solution of sodium carbonate. 
It is a greenish-yellow liquid, having a slight odor of chlorine and a 



DISINFECTANTS 057 

slurp saline taste. It contains, among other substances, sodium 
hypochlorite, and possesses i lu> therapeutic and disinfectant proper- 
ties of the chlorinated compound. Owing to its liquid form, its com- 
parative freedom from odor, and its depositing sodium chloride on 
evaporation, it is the most elegant of all the chlorine preparations for 
use in the sick-room. 

Compound Solution of Chlobine, which replaces the old chlo- 
rine water, is made by adding hydrochloric acid to a solution of potas- 
sium chlorate, and should contain 0.4 per cent, of chlorine with some 
chlorine peroxide. 

When chlorine is brought into contact with organic substances 
and moisture, it unites with the hydrogen of the water and liberates 
nascent oxygen, which rapidly oxidizes and destroys the organic 
compound. When chlorine comes in contact with sulphuretted 
hydrogen, it removes its hydrogen and thereby destroys it. On 
account of its destructive action on organic matter, its being extremely 
obnoxious to animal life, and its comparative expensiveness, chlorine 
gas is at present never used to disinfect rooms, ships' holds, or similar 
places. Inspired in sufficient amount, chlorine gas produces, both 
in man and in the lower animals, narcotism, and finally death from 
paralysis of the respiratory centre.* The germicidal influence of 
chlorine is very great. 

Fisher and Proskauer found that dried anthrax spores maintained their integrity 
for one hour when exposed to the action of a dry chlorine atmosphere containing 
44.7 parts of chlorine in 100; but when the air and the spores were moist, one hour's 
exposure to an atmosphere containing four per cent, of chlorine produced complete 
disinfection. If the exposure were continued for three hours, one per cent, of chlo- 
rine was an efficient germicide; and if the spores were exposed for twenty-four hours, 
the effective proportion of chlorine could be still further reduced. In Sternberg's 
experiments, six hours' exposure of vaccine lymph dried upon ivory points to an 
atmosphere containing 1 part of chlorine in 200 was sufficient to destroy the infec- 
tive property of the lymph, while the bacteria of putrid urine were destroyed after 
six hours' exposure to an atmosphere containing 1 part of chlorine in 400. Klein 
also found that after the compartment of a stable in which pigs had died of swine- 
plague had been thoroughly fumigated for six hours with chlorine, healthy animals 
could be placed therein with safety. 

The result of all our knowledge upon the subject of the disinfectant 
properties of chlorine, iodine, and bromine has been summed up by 
George H. Rohe as follows: 

1. Chlorine is an efficient disinfectant when present in the proportion of 1 part 
in 100, provided the air and the objects to be disinfected are in a moist state and 
the exposure continues for upwards of an hour. 

2. Chlorine, when used in sufficient concentration to act as a trustworthy 
disinfectant, injures colored fabrics and wearing apparel. 

3. Bromine is an efficient disinfectant in the proportion of 1 part in 500, 
provided the air be in a moist state and the exposure continues for upwards 
of three hours. 

4. Iodine, in solution, is an efficient disinfectant in the proportion of 1 part in 
500, the exposure continuing for two hours. 

* Consult Arch. f. Exper. Path. u. Pharm., xiii. 
42 



658 



EXTRANEOUS REMEDIES 



5. The use of chlorine, and in a greater degree of bromine, requires consider- 
able experience in management: when carelessly handled these elements may cause 
inconvenient or even dangerous symptoms in persons using them; hence they are 
not suitable as disinfectants for popular use. 

The experiments of J. R. Duggan indicate that the hypochlorites 
are among the very best of our practical germicides. He found that 
0.25 of one per cent. (1 part to 400) of chlorine as hypochlorite is an 
effective germicide even when allowed to act for only two minutes; 
while 0.06 of one per cent. (6 parts to 10,000) will kill the spores of 
B. anthracis and B. subtilis in two hours. 

According to Duggan, a two-per-cent. solution of sodium hypo- 
chlorite, representing six per cent, of available chlorine, will kill the 
anthrax spores in thirty minutes. Sternberg found that it required 
seven per cent, of a commercial Labarraque's solution to kill, the 
anthrax spores in two hours. It must be remembered that the com- 
mercial preparations of both chlorinated lime and chlorinated soda 
vary enormously in strength. The Committee on Disinfection of 
the American Public Health Association, 1885, found that commercial 
specimens of Liquor Soda Chlorinate varied in the amount of avail- 
able chlorine from 3.8 to 0.01 per cent, and chlorinated lime from 
33.5 to 24.1 per cent, of available chlorine. 

Therapeutics. — Bleaching-powder usually contains from twenty- 
five to forty per cent, of available chlorine. For most purposes, a 
solution made with 1 part of this preparation to 100 parts of water 
is strong enough, for it will contain from 0.25 to 0.04 of one per cent, 
of chlorine as hypochlorite. As is stated above, the smaller of these 
quantities is sufficient to destroy spores almost instantly. There are 
very few purposes to which disinfectants are applied that are not 
fulfilled by this solution of 1 to 100 of bleaching-powder. It is not 
dangerously poisonous, is said not to injure (although of course it 
bleaches) the fibre of clothing, bedding, etc., and is very cheap, since 
it is worth only about five cents per pound. For the destruction of 
disease-germs in urine, fecal discharges, sputum, etc., a saturated 
solution of bleaching-powder appears to be in all respects the best dis- 
infectant known: for the purification of cesspools, sewers, or similar 
receptacles, or of masses of infected filth, chlorinated lime stands at the 
head of known germicides.* 

Internally chlorine has been used in various diseases, especially in 



* There are not many affairs in life in which the public have been so superabundantly fleeced 
as in the matter of disinfection. A most extraordinary part of this swindling is the ease with 
which distinguished members of the medical profession have given certificates of efficiency and 
value to comparatively inert and extraordinarily expensive proprietary compounds. Oddly 
enough, the cat that has drawn the chestnuts out of the fire for avaricious manufacturers has not 
even had the sense to smell the odor of its own paws when burning ! There is no proprietary dis- 
infectant whose value corresponds with its selling price. 

H. C. Wood, Jr., compiled for the 12th edition the following table on the basis of one cent'* 
worth of corrosive sublimate. 



Name. Full Cost. 

Mercurv bichloride SO. 01 

Chlorinated lime 0.00J 

Cresol 0.06 

Bacillol 0.24 

Lysol 0.23 



Name. Full Cost. 

Creolin $0.50 

Piatt's chlorides 3.19 

Sanitas 11.72 

Listerine 62.81 



I)|S[ NKKCTA NTS 



659 



malignant typhus, but at present is rarely if ever so employed. 
It is occasionally used as an intestinal antiseptic in enteric fever. 
It is stated to be stimulant and tonic to the stomach, and is thought 
by some to have an especial influence upon the liver. It has been 
employed in chronic hepatic affections; either the compound solution 
of chlorine or the solution of chlorinated soda, properly diluted, may be 
employed. Chlorine water is a powerful irritant, capable of produc- 
ing severe inflammation of the skin or toxic g astro-enteritis. Properly 
diluted, it forms an excellent stimulant, disinfectant, detergent wash 
for foul ulcers, and may be used as a gargle in malignant sore throat. 

Fluorides. — Hydrofluoric acid gas, dissolved in water, — i.e., commercial 
hydrofluoric acid, — is a powerful corrosive which hardens the skin or tissue with 
which it comes in contact and continues to penetrate, producing great pain. It is 
not itself used at all in medicine, and is probably unfit for any therapeutic purposes. 

According to Tappeiner and to Waddell, the alkaline fluorides are not 
extremely irritant, and when taken in doses of from one to one and a half grains are 
depressants to the circulation, especially affecting the vaso-motor centres. They 
have been used to some extent in various diseases, but have given no promise of 
usefulness unless it be in the treatment of goitre. 

As germicides the fluorides have been used in various forms. Under the name 
of Fluorol, the sodium fluoride has been employed in a two-per-cent. solution for 
the treatment of infected wounds. The silver fluoride, Tachiol, is a feeble coag- 
ulant of albumin, but is affirmed by Durante and Perez to be in 1 : 1000 an effective, 
very penetrating, not pronouncedly irritant, germicide which may be used in 
various local affections. 

Recently, various organic fluorides have been put upon the market. Accord- 
ing to Tischer and Beddies, they are antispasmodics and bactericides. 

Di-fluor-di phenyl, a white aromatic powder, insoluble in water, freely soluble 
in alcohol, has been recommended as a ten-per-cent. dusting-powder or a ten-per- 
cent, ointment, by J. Thimm in the treatment of syphilitic ulcerations. Its five-per- 
cent, ointment has been exploited as Antitussin, as useful when appb'ed locally in 
whooping-cough. 

Xeodermin is a five-per-cent. ointment of fluor-pseudocumol, said to act like 
Antitussin. 

Fluoroform, affirmed by Binz to have properties somewhat similar to chloro- 
form, has been put upon the market under the name of Fluoroformol, in the form 
of a two- and eight-tenths-per-cent. aqueous solution, which is almost odorless and 
tasteless, and is said to be non-toxic and non-irritant. It has been used in internal 
tuberculosis in doses of one drachm four or five times a day, but, according to Gorl, 
is of very little value. 



The following table was compiled some years since by A. W. Harlan, of Chicago. The cost 
represents the same germicidal power. In comparing these tables it should be remembered that 
the constitution of some of these proprietary disinfectants has entirely changed. 



Name. 

Corrosive sublimate 

Chlorine 

Copper sulphate 

Mercury biniodide 

Mineral acids 

Bromine 

Chloroform 

Potassium chlorate 

Silver iodide 

Picric acid 

Iodine 

Silver nitrate 

Potassium permanganate. 

Carbolic acid 

Benzoic acid 

Salicylic acid 



Full Cost. 



SO 



00 A 

oiA 

.III.-, 

.02$ 
.03* 

ns 

.144 

.If..'. 

.20 

.208 

.2)8 

224 
.30* 
•34J 
.56 



Name. 

Corrosive sublimate 

Thymic acid 

Little's sol. phenyl 

Fifty per cent, ohlor. zinc, Squibb's. 

Feuchtwanger's disinfectant 

PhCnol sodique (Hanco Bros. & 

White) 

Piatt's chlorides 

Girondin 

Williamson's sanitary fluid 

Bromo-chloralum 

Blackmail's disinfectant 

Squibb's solution impure phenol 

Burchardt's disinfectant 

Phenol sodique, French 

Listerine 



Full Cost. 
$0.00 A 

. 4.80 
13.00 
35.00 
35.00 

51.00 

66.00 

80.00 

80.00 

80.00 

96.00 

112.50 

182.50 

255.00 

495.00 






660 EXTRANEOUS REMEDIES 

IV.— OXIDIZING DISINFECTANTS. 
POTASSIUM PERMANGANATE. 

This salt occurs in slender, prismatic crystals of a dark purple 
color, inodorous, of a sweetish, disagreeable taste, and forming with 
water a solution varying from a purplish black to a beautiful reddish 
lilac, according to the strength. When kept dry, and not exposed 
to the atmosphere, potassium permanganate is a permanent salt, 
but whenever in solution it is brought into contact with an organic 
body it at once gives up its oxygen to the latter and is converted 
into potassa and black manganese oxide. 

The statements concerning the germicidal power of potassium 
permanganate differ very materially. 

Sternburg, in one series of experiments, found that 0.12 per cent, solution 
would kill the pus cocci in two hours and was equivalent to 0.8 per cent, solution 
of phenol. In a second series of experiments the same author found that it required 
a two-per-cent. solution to destroy the infection of mouse septicemia as compared 
with a 1.2 per cent, solution of carbolic acid. According to Koch, a five-per-cent. 
solution will destroy the anthrax spores in one day. 

The difference in the results of experimenters has been shown by 
Sternberg to depend upon the amount of organic material present: 
when this is large, the salt is so rapidly destroyed by the organic 
material that it has no chance to act upon the contained micro- 
organisms. 

Therapeutics. — Potassium permanganate affords a very ele- 
gant disinfectant and germicidal wash for wounds, ulcers, abscesses, 
fetid ozccna, otorrhoea, leucorrhoea, etc. In dilute solution its local 
influence is stimulant and beneficial. When employed in the form 
of powder it even affects living tissues, acting as a mild caustic, 
and, as such, may often be applied with advantage to sloughing 
ulcers. As a wash, the strength may vary from one to twenty grains 
to the ounce. 

P. W. Mac Donald has found the potassium permanganate to be 
very effective in dysentery. As soon as the diagnosis is reached, the 
whole of the lower intestine should be washed out, night and morning, 
with a solution of potassium permanganate (from two to four grains 
to a pint). 

The injection of a strong solution of potassium permanganate in 
the immediate neighborhood of snake-bites is said to be very effective. 
The action of the permanganate in these cases is that of a destructive 
oxidizant. 

In a series of laboratory experiments we have determined that 
potassium permanganate is capable of destroying many alkaloids, 
acting very rapidly upon cocaine and morphine, but slowly upon 
strychnine, and Fodera has found it antidotal also to helleborein 
and veratrine. We have also found that, as was first pointed out by 
William Moor, administered shortly after the alkaloid it is of prac- 



DISINFECTANTS 66] 

tical value in morphine-poisoning. These results are in accordance 
with those obtained by other experimenters, and with numerous 
recorded cases of opium-poisoning.* The permanganate should be 

given in small doses by the mouth at intervals during the acute stage 
of opium-poisoning, as it has been shown that there is a continuous 
excretion from the walls of the stomach of morphine, which is 
subsequently reabsorbed either from the stomach or intestines. 

HYDROGEN DIOXIDE. 

The official Solution of Hydrogen Dioxide (Aqua Hydrogenii 
Dioxidi) is a colorless, odorless, slightly acid, aqueous solution of 
hydrogen dioxide (H 2 2 ) containing, when freshly prepared, about 
three per cent., by weight, of the pure dioxide, corresponding to 
about ten volumes of available oxygen; a small amount of free acid f 
is always left in it as a preservative. It is apt to undergo decom- 
position, and should be kept in a cold place, and not too tightly 
stoppered, particularly in hot weather, lest there should be such a 
brisk evolution of oxygen in a confined space as to cause an explosion. 
Hydrogen dioxide has been employed to a considerable extent in the 
arts for bleaching and cleansing human hair, engravings, very fine 
textile fabrics, etc. 

The original statement of B. W. Richardson, that hydrogen 
dioxide is a powerful oxidizant of organic matters, is undoubtedly 
correct. It is an active coagulant of albumin, and when brought in 
contact with mucous membranes or ulcerated surfaces evolves gas, 
at the same time forming a dense white coating. With pus it effer- 
vesces very actively, and rapidly destroys the corpuscles, which 
immediately become granular, lose their shape, and break up 
into detritus. It is also a powerful deodorant, quickly oxidizing 
hydrogen sulphide and similar gases. Further, it is a very powerful 
germicide. 

Pane states that he has demonstrated that hydrogen dioxide in 
a solution of 1 to 100 has an energetic germicidal power, and that 
solution of H 2 2 , in nutritive substances, 1 to 352, not only impedes 
the development, but after some days kills the spores of the bacillus 
of charbon. Sternberg, however, believes the germicidal value of 
hydrogen dioxide has been greatly overestimated. He experimented 
with a solution of hydrogen dioxide containing 4.8 per cent, of H 2 2 
and five per cent, of sulphuric acid. In his experiments this solution 
in the strength of twenty per cent, (representing 0.8 per cent. H 2 2 ) 

* Moor (Therapeutiache Monatshefte, 1903, vol. xvii., page 5G2) asserts that potassium per- 
manganate forms with albumin a substance which has the power of destroying morphine, and 
concludes, therefore, that the permanganate is capable of following and neutralizing the poison 
in the blood. The chemical evidence, however, of his conclusions is not satisfactory, and we have 
found that the hypodermic injection of the permanganate in the lower animals does no good what- 
soever in morphine-poisoning. Fodera asserts that the hypodermic injection of potassium per- 
manganate has a certain antidotal value to morphine and strychnine even when injected at a 
distant point, but that if the alkaloid is injected before the potassium permanganate, the 
antidote has no effect upon the course of the poisoning. 

t The existence of this free acid endangers the teeth when the Hydrogen Dioxide Solution 
is used habitually as a tooth-wash. 



662 EXTRANEOUS REMEDIES 

killed the anthrax spores in two hours, and ten per cent, of this solu- 
tion destroyed the pus cocci in the same time: these effects Stern- 
berg believes were largely due to the sulphuric acid, which he has 
found will destroy the pus cocci in two hours in proportion of 1:200. 
On the other hand, Gifford found that an almost neutral fifteen-per- 
cent., by volume, solution of hydrogen dioxide (about four per cent, 
by weight) destroyed the anthrax spores in five minutes and the pus 
cocci in one to two minutes. This solution diluted with four parts of 
water (0.S per cent. H 2 2 ) failed to kill the pus cocci in thirty minutes. 
Gifford asserts that the bactericidal effect of hydrogen dioxide does 
not depend upon the liberated oxygen, and that the presence of 
large amounts of organic matter rapidly decomposes the agent and 
interferes with its germicidal properties. 

Therapeutics. — The cost of hydrogen dioxide is entirely too 
great to permit the use of it as a general antiseptic, or, as has been 
proposed, for the purification of water. On the other hand, for some 
of the purposes of the surgeon it is invaluable, its liquid form making 
it especially adapted to the cleansing and disinfection of putrid 
cavities, deep infected wounds, abscesses, etc. Its influence is always 
immediate and fugacious, so that it cannot replace other antiseptics 
for the permanent dressing of wounds. Theoretically, it is capable 
of being used for the disinfecting of hands and instruments. 

As a local application in specific inflammations of mucous mem- 
branes hydrogen dioxide is of the greatest value. In scarlet fever 
and diphtheria the official solution may be applied by mop to the 
pharynx, often with extraordinarily good results. Diluted one-half, 
it may be injected into the nasal cavities when they are affected. 
Injection of a solution of from twenty per cent, to full strength has 
received commendation in the treatment of gonorrhoea and chancre. 
The official solution has also been used with alleged great success as 
a local styptic. As a local application to mucous membranes, the 
official solution may be used; the stronger solutions are sometimes 
too irritating. 

As an internal remedy, hydrogen dioxide was strongly recom- 
mended by John Day in diabetes, low fever, and other typhoid condi- 
tions. On account of its non-absorbability, however, it is probably 
of no value as a systemic remedy in these or any other diseases. 

In H. C. Wood's experiments hydrogen dioxide was found, when 
injected intravenously, to produce immediate wide-spread coagula- 
tion of the blood; and put into the stomach in solution it must 
destroy itself by acting upon the organic contents and secretions. 
It is certain that death has been caused both in the lower animals 
and in man by injecting the solution into the pleural or peritoneal 
cavity. It has seemed to us probable that these deaths were due 
to shock, the outcome of the intense local irritation of the pleura 
or peritoneum, but the cases reported by E. G. Janeway suggest 
that they have been caused by embolic arrest of circulation in the 
nerve-centres. 



DISINFECTANTS 663 

in the case reported by Laaoh, bix injections into the pleural oavity, each 0011 
taining 0.8 cubic centimetre of a three-per-oent. solution of hydrogen dioxide, 
were administered, bu1 al the seventh the patient complained of f:iintiu\ss, the pul c 
failed, respiration became oppressed, and death occurred in ten minutes. In E. (!. 
Janeway's case collapse with temporary hemiplegia followed immediately upon the 
injection of hydrogen dioxide into a sacculated empyema, it must be remembered, 
however, that there are on reeord a number of eases in which injection of simple 
water into the pleura has produced collapse, paralysis, or convulsions; so that it 
appears doubtful whether, after all, the hydrogen dioxide itself and not. the fluid 
containing it has been the cause of the symptoms in the case just alluded to. On 
the other hand, probability is lent to the theory that the symptoms above spoken 
of are due to emboli by the statements of Colasanti and Brugnola, that hypodermic 
injections of the dioxide rapidly kill the rabbit by causing general gaseous oxygen- 
emboli; that in the dog they produce a local emphysema, followed by convulsions, 
urobilinuria, and other disturbances. 

Benzotl-Acettl-Peroxide. — Benzozone. — Acetozone. — The pure peroxide 
occurs in a white crystalline mass, slightly soluble in alcohol; prone to undergo 
decomposition spontaneously, and capable when heated in a confined space, or 
when powdered or ground, of exploding. It is slowly dissolved and decomposed 
by water, and in contact with alkaloids and organic matters of all kinds it 
undergoes rapid change with oxidation of the decomposition substances. 

Acetozone is the benzoyl-acetyl-peroxide diluted with a neutral drying powder, 
so that it contains fifty per cent, of the pure drug. Fifteen grains of the pure drug, 
or thirty grains of the commercial drug, may be dissolved in one and a half gallons 
of water, thus forming an active solution which must, however, be used within 
thirty-six hours after making. Benzoyl-acetyl-peroxide is an active germicide; 
experiments in the laboratories of the United States Government in the Philippines 
show that one part of the hydrolized substance to 177 of water, containing only 
0.0.5 per cent, of active oxygen, destroys all germs, including spores, almost instantly, 
and even at a dilution of 1 : 3000 vegetating germs, as a rule, are killed within one 
minute, but the spores require a longer time. On comparing these results with 
similar ones with hydrogen peroxide, 1: 1000, and phenol 5 per cent., it was shown 
that hydrogen peroxide, although it contained ten times as much active oxygen 
as the solution of benzoyl-acetyl-peroxide, was by no means as effective, and the 
same may be said of phenol. It was further shown that one part in a thousand 
absolutely destroys, and that one to thirty thousand distinctly inliibits, the growth 
of the comma bacilli. In the experiments of the discovery of acetozone (Feer and 
Novy), one drachm of it a day given to a dog weighing eight kilos for weeks produced 
no sensible effect, and it is probable that it is not taken into the blood at all. Charles 
L. Bliss states that the peroxide is eliminated in the form of hippuric acid. 

Benzoyl-acetyl-peroxide has been used in the United States Philippine hospitals 
as an intestinal germicide with most excellent results in cholera, given in double 
capsules in doses from 0.2-0.32 gramme (4-5 grains) every two to four hours. It 
was found that when the stomach was full at the time of administration vomiting 
frequently occurred, probably due to the decomposition of the peroxide by the 
organic matter present, since no irritation was produced when the stomach was 
empty. Benzoyl-acetyl-peroxide has been employed primarily by Wasdin, and 
subsequently by Harris and others in typhoid fever, with alleged most extra- 
ordinary results in the reduction of the local and general symptoms, — one 
hundred and thirty to two hundred and ten grains being administered in the 
twenty-four hours. 

Acetozone has been used locally as a germicide with alleged excellent results 
in gonorrhoea, malignant wdema, tinea tonsurans, infected ulcers, and similar affec- 
tions. In surgical cases the dry acetozone may be applied directly to the wound. 
When it is desired to especially affect the intestinal tract, the drug should be given 
in double capsules so as to insure as far as may be its entrance unchanged into the 
duodemun. 



664 i:\TRANEOUS REMEDIES 

V.— CARBON COMPOUNDS. 
PHENOL. 

Phenol (Carbolic Acid, Phenylic Alcohol, Hydroxybenzene) is 
a substance obtained from coal-tar by distilling at a temperature of 
between 300° and 400° F., adding to the distillate a hot concentrated 
solution of potassium hydroxide, and, after this, water, separating 
the light oily matters which rise to the top, and adding hydrochloric 
acid to the heavy alkaline bottom layer, when impure carbolic acid 
separates. This impure carbolic acid is of a dark color, and contains 
several congeneric bodies, especially xylic and cresylic acids. These 
acids are as active germicides as is phenol, so that crude carbolic 
acid is very largely used. 

The official phenol should contain at least ninety-six per cent, 
of absolute phenol. It occurs at ordinary temperatures in minute, 
colorless, transparent plates, or long rhomboidal needles, often fused 
into a mass, having a hot, corrosive, peculiar taste and odor, 
resembling but decidedly different from those of creosote. When 
opportunity is afforded, solid carbolic acid absorbs water from the 
atmosphere and melts into an oily-looking, colorless liquid. It is 
inflammable, neutral to test-paper, but combines with bases; soluble 
in about twenty parts of water, very soluble in alcohol, acetic acid, 
ether, glycerin, and the volatile and fixed oils. Nitric acid converts 
it into picric acid. 

Official Preparations: 

Phenol [Carbolic Acid] 1 to 2 grains (0.06-0.13 Gm.). 

Phenol Liquefactum (86.4 per cent.) 1 to 2 minims (0.06-0.13 Gm.). 

Glyceritum Phenolis (16 per cent.) 5 to 10 minims (0.3-0.6 C.c). 

Unguentum Phenolis (3 per cent.) [Carbo- 

lated Vaseline] External use. 

Physiological Action. — Local Action. — In concentrated form 
carbolic acid is a mild escharotic, its momentary application to the 
sound skin producing burning pain and a white discoloration which 
changes to a reddish stain, gradually fading away as the skin 
desquamates. If the application be prolonged an eschar forms. 

Carbolic acid in sufficient concentration is poisonous to all forms 
of protoplasm; thus, even its weak solution arrests the movements 
in ciliated cells and in white blood-corpuscles (T. M. Prudden, Labee). 
It appears, however, to act especially upon the central nervous 
system and upon the peripheral nerve-endings: as was simultaneously 
pointed out by Erasmus Wilson and J. H. Bill, it is a local anesthetic. 

Phenol is one of the oldest and one of the most popular of all 
germicides, but its power and reliability are usually overestimated. 

According to Van Erlingen, a five-per-cent. solution destroys the viability 
of anthrax spores after thirteen days' exposure. On the other hand, Koch has 
found that a three-per-cent. solution of phenol will destroy the anthrax spores in 
two days. According to Nocht, the activity of carbolic acid varies very greatly at 



DISINFECTANTS 865 

different temperatures. Thus al room temperature a five-per-cent. solution failed 

to destroy t he anthrax spores alter several days' exposure, bul when kept al a 
temperature of 37.5° C. the same solution was sufficient in three hours. It is evi- 
dent, however, that the common statement that five-per-cent. solution of phenol 
is equivalent to 1:1000 of corrosive BUblimate is not true, since the 1:1000 
solution of corrosive sublimate will destroy the viability of the anthrax spores 
in two or three minutes. 

Of the loss resistant germs, phenol is an efficient destroyer. 

Thus, Burgess found that a 1:40 solution destroyed the bacillus coli communis 
m five minutes, corresponding to 1:2000 corrosive sublimate solution. In Stern- 
berg's experiments 0.8 per cent, destroyed the pus cocci in two hours' exposure. 
Boer has determined that in the absence of spores I :.'!()() solution is efficient against 
the anthrax bacillus in two hours. 

Absorption and Elimination. — Phenol is readily absorbed through 
the gastro-intestinal mucous membrane as well as through the skin. 
Hoppe-Seyler found it in the blood, where it probably circulates as 
an alkaline carbolate and also uncombined. It is rapidly eliminated, 
having been detected in the urine by Alm6n, by Patrouillard, by 
Salkowski, by Hoppe-Seyler, by Waldenstrom, and by Hauxmann: 
Hoppe-Seyler detected it in the saliva, and it probably occurs in all 
the secretions. The researches of Baumann, which have been sub- 
stantially confirmed, show that the phenol is changed into phenol- 
sulphonic acid [C H 5 O.SO,.OH], which finally unites with alkalies 
and is eliminated as a phenolsulphonate. Portions of it are also 
excreted as glycuronic acid, hydrochinone and other oxidation com- 
pounds. The black coloring matter of the characteristic urine of 
phenol-poisoning is in all probability an educt from phenol, formed 
by its partial oxidation. When large quantities are administered, 
some of it escapes unchanged. 

In a fatal case of poisoning Patrouillard obtained an oily fluid, believed to be 
pure carbolic acid, by shaking the urine with ether, allowing the mixed fluids to 
separate, and removing the ethereal layer and evaporating. 

Hauxmann has proved that this black coloring matter is not altered hematin or 
any fixed coloring principle, by finding that the urine is cleared up by heating after 
the addition of an acid; and his conclusion is corroborated by the observation of 
Stevenson, of Guy's Hospital, who determined that the black urine does not contain 
more than a normal proportion of iron. When carbolic acid is oxidized outside of 
the body, as by the action of potassium permanganate, oxalic acid is formed; and 
Salkowski has shown that when phenic acid is given to animals oxalic acid appears 
in the urine. Other observers have, however, failed to detect Hirse oxalates. Fr. 
Schaffer, A. Uerbach, and E. Baumann and C. Preusse found that the phenol was 
at least in part oxidized into hydrochinone and partly into a greenish-black sub- 
stance upon which the coloring of the urine seems to depend. The researches of 
L. Brieger led him to the conclusion that when phenol is taken in not too large 
quantities a portion of it unites with sulphuric acid and a portion of it is converted 
into various colored oxidation products, some of which are very poisonous. Accord- 
ing to the experiments of W. Kochs, this change occurs in the large abdominal 
glandular viscera. 

Schmiedeberg has come to the conclusion that no phenol is oxidized in the 
body, but that it is all eliminated in combination with sulphuric acid, or to 



666 EXTRANEOUS REMEDIES 

a less extent with glycuronic acid. Reale affirms that when the sulphuric acid 
lias all been appropriated phosphoric acid is attacked by the phenol and a 
phospho-carbolate formed. 

Production of phenol in the Animal. — Stadeler discovered that when sulphuric 
acid was freely added to cow's urine the latter yielded upon distillation phenol, 
and concluded therefrom that normal urine contains carbolic acid. He has been 
corroborated by Buliginsky and by Hoppe-Seyler; so that phenol is certainly a 
constituent not only of the urine of cattle, but also of that of men, dogs, horses, 
and probably other animals. Baumarm has succeeded in producing phenol out of 
fibrin by a protracted digestion with the pancreatic glandular substance, and Nencki 
and Brieger have found that it is constantly present in normal human feces. Its* 
elimination by the urine is enormously increased in ileus (one-hundredfold, Salkow- 
ski), and diminished in anemia, phthisis, scorbutus, scrofula, and cancer (Brieger). 
It is quite possible that the phenol is formed in the intestine by fermentative changes, 
as Baumann has noticed the closely allied substance indol produced by the putre- 
factive changes in a mixture of albuminous substance with a small quantity of 
pancreas and a little ammonium carbonate. In this connection it is interesting to 
note that Christiani has not been able to find phenol in the urine of chickens fed 
upon vegetable diet, although a notable amount is present when a flesh diet is 
allowed. In a series of experiments I. Munk obtained three grammes as the 
average excretion of twenty-four hours from a horse. 

General Effects. — The largest therapeutic doses of phenol produce 
no distinct symptoms. Reserving the details as to the effects of 
toxic doses for the section on toxicology, it is sufficient for our pres- 
ent purpose to state that the prominent symptoms induced by lethal 
doses are disturbance of respiration, stupor deepening into coma, 
rapid, feeble pulse, muscular weakness, abolished reflexes, collapse, 
fall of temperature, and albuminous or bloody urine, ending in death 
from central paralytic asphyxia. In some cases convulsions occur. 

According to Isidor Neumann, to Ernest Labee, and to Salkowski, a poison- 
ous dose of phenol causes in the frog a paralysis which usually affects first the hind 
legs,* but eventually spreads to the front legs and involves all parts of the body. 
After a time there are developed tetanic convulsions, which are apparently reflex 
in their nature, and are said to be excited by external stimuli or irritations. 

Upon mammals phenol acts in very much the same way as it does upon the 
batrachian. According to W. Kempster, in the mouse and rat it causes intense 
muscular weakness, followed by violent convulsions and stupor. In the rabbit 
(Neumann, Salkowski) phenylic alcohol produces muscular weakness, often 
accompanied by tremblings and restlessness, at last giving place to violent con- 
vulsions. As has been pointed out by Turtschaninow, the tremors first commence 
as peculiar tremulous contractions of isolated muscles, and then of muscle groups 
which are irregular, and not at all symmetrical. Early in the poisoning the respi- 
ration is affected; and death, which usually occurs in the midst of convulsions, 
is owing to a paralysis of the respiration, since in acute cases the heart is found 
beating continuously immediately after death. According to the researches of 
Jules Lemaire, in the dog symptoms very similar to those detailed above are caused 
by lethal doses of the drug; and Husemann states that in mammals and in birds 
the characteristic phenomena of phenol poisoning are clonic convulsions, sinking 
of the temperature, diminution of sensibility, dyspnoea, free salivation and 
secretion of tears, keratitis, and conjunctivitis. According to the latter authority, 
albuminuria and hematuria are occasional phenomena. 

* According to Lemaire when a frog is allowed to swim in water impregnated with phenol, 
the front legs are first affected. 



DISINFECTANTS 667 

Phenol, being a universal poison, acts upon the whole system; 
so that the detailed study of its physiological effects when given 

internally is simply an endeavor to determine what tissues are most 
susceptible to its influence. 

Nervous System. — The influence of phenol on the cerebrum is 
not very intense in the lower animals, but in the higher species, and 
especially in man, results in the early production of stupor. 

The convulsions are not peripheral, since they do not occur in 
a limb whose connection with the spine has been severed by division 
of the nerve, and do take place in a leg which has been protected 
against the local action of the poison by tying the artery (Salkowski, 
Labee). They are, therefore, either cerebral or spinal. Although 
there is a distinct conflict of evidence, it seems established that the 
convulsions are of spinal origin. After large doses there is developed 
later a paralysis of the spinal motor centres. 

Labee and J. R. Haynes failed to get them after section of the cord, but in the 
far more numerous experiments, upon frogs and mammals, of Salkowski, of Berb 
and Jogel, of J. S. Stone, and of T. Gies, convulsions occurred after destruction 
of the medulla, section of the cord, and other operative procedures separating the 
brain from the lower nervous system. The failures of the first -named experiments 
are explainable by the facts that the paralyzing influences of phenol are usually 
first manifested upon the hind legs, and that very large doses were employed. 

In phenol-poisoning the nerves and muscles are not distinctly paralyzed (Sal- 
kowski, Hoppe-Seyler), but the very careful experiments of Gies have proved that 
the muscles are less sensitive and more easily exhausted than is normal. 

Circulation. — The action of phenol upon the heart is not a very 
marked one, but there can be little doubt that in sufficient amount 
the drug depresses the heart and perhaps also the vaso-motor centres. 

After death from acute poisoning the heart is usually foimd to be beating regu- 
larly (Salkowski), but in some cases of slow poisoning the death lias seemed to be 
ultimately caused by cardiac diastolic arrest. In Hoppe-Seyler 's manometrical 
studies the arterial pressure was not affected until convulsions came on, when it 
rose from the effects of the general muscular contraction. It afterwards fell very 
decidedly and permanently. 

Reduction of the arterial pressure has been shown by Gies to be the charac- 
teristic effect of the phenol: in his experiments moderate doses of phenol failed 
to affect the pressure after section of the cord, while in the normal animal neither 
asphyxia nor stimulation of a sensitive nerve elevated the lowered pressure, although 
the heart was beating forcibly — facts that demonstrate that phenol paralyzes the 
vaso-motor centre in the medulla before it markedly affects the heart. 

Respiration. — According to Salkowski, Labee, and other author- 
ities, in the first stages of phenol-poisoning the respiration is remark- 
ably increased in frequency. This acceleration Salkowski believes 
to be due partly to a stimulant action upon the peripheral vagi and 
partly to a similar influence upon the respiratory centres. The final 
paralysis of respiration by phenol is almost certainly due to a direct 
action upon the respiratory centres. 

Salkowski states that the respirations are very shallow, and that the diaphragm 
scarcely participates at all in them, but that if the cervical vagi be cut they become 



668 EXTRANEOUS REMEDIES 

much slower, deep, and regular. On the other hand, if phenol he given to an animal 
suffering from section of the pneumogastrics, the slow breathing is very much acceler- 
ated. From the former of these facts the German investigator draws the conclusion 
that the accelerated breathing produced by phenylic alcohol is in part due to a 
stimulation of the peripheral vagi, and from the latter fact that it partly arises 
from a similar action upon the respiratory centres. 

Temperature. — According to the researches of Hobart A. Hare, 
phenol injected into rabbits produces a very distinct fall in the bodily 
temperature, which is usually, but not always, coincident with the 
lowering of the arterial pressure. In the calorimetric studies made 
by Hare the action upon heat-production and heat-dissipation in 
the normal animal appeared to be various, sometimes production 
and sometimes dissipation being alone affected, while in other cases 
both functions were altered. Some years ago Emil Erls found that 
in mild putrid poisoning in animals phenol diminished greatly the 
fever-heat; when the poisoning was more severe it had no influence. 
The calorimetric studies made by Hare upon fevered animals were 
fairly constant in their results, although the method of experimenta- 
tion was not satisfactory, because the drug was given to the fevered 
animals at a time when it was uncertain what would have been the 
production of heat without its influences. Nevertheless, the experi- 
ments indicate that phenol may affect the thermogenetic functions 
of the body in two ways: first, by diminishing the production of 
heat; second, by increasing the dissipation of heat. 

Therapeutics. — In the doses in which it is usually given, 
phenol exerts no perceptible effect upon the system. It has been 
used to a considerable extent in zymotic diseases for the purpose of 
destroying the germs in the blood, but is of no value for such purpose. 
There is no reason for believing that micrococci or bacteria are more 
sensitive to its action than is the human organism; and clinical 
experience in zymotic diseases has certainly demonstrated the 
uselessness of the drug. 

The use of phenol in tetanus, as original^ proposed by Baccelli, 
has in a number of cases been attended by apparently beneficial 
results. Ascoli has collected thirty-four cases with only one death. 

Exactly how phenol acts has not been determined; Heddaeus believes that it 
neutralizes the toxin in the same manner as does the antitoxin. It is to be given 
hypodermically in the form of two-per-cent. solution, from five to fifteen grains 
(0.3-1 Gm.) in the twenty-four hours. (See H. C. Wood, Jr.) Courmont and Doyon 
in a research upon mice, guinea-pigs, and rabbits found that in these animals 
carbolic acid is useless against tetanus infection. 

For its local effects, phenol is a very valuable remedy in the treat- 
ment of various forms of nervous irritability of the gastro-intestinal 
mucous membranes, especially when there is also a tendency to 
fermentative changes in the food, as the result of imperfect digestion. 
In nervous vomiting, and in gastrodynia, it may be given in doses of 
from one to two grains, repeated at intervals varying from fifteen 
minutes to two hours, according to the symptoms of the case. In 



DISINFECTANTS 660 

diarrhoea of irritation, as well as of relaxation, it is often of the greatest 
service. The combination of one or two grains of phenol with ten 
to twenty grains of bismuth subearbouate, given in emulsion or in 
capsules, is one of the most generally useful of diarrhoea mixtures. 11 
In gangrene of the lungs the internal administration of carbolic acid 
combined with the use of a weak solution, ten grains to the fluidouncc, 
by atomization, is said to be of great service. The use of carbolic 
acid as an antipyretic, as inaugurated by H. ftl. Desplats, has not 
found favor, and is scarcely justifiable. 

The external use of phenol belongs to the domain of surgery 
rather than of medicine, and we shall discuss it very briefly. As a 
caustic, phenol is not available when large masses of tissue are to be 
destroyed, but it may often be employed with advantage against 
condylomata and similar growths. Even in such cases, to be efficient, 
it must be in the most concentrated form. In diphtheria, ulcerated 
sore throat, and aphthous stomatitis its concentrated solution in glycerin 
may carefully be applied, by means of a camel's-hair brush or a mop, 
as a mild caustic scarcely capable of destroying sound tissue. In 
various forms of indolent ulcer and in ill-conditioned wounds phenol 
affords a very useful stimulant application; in burns, properly diluted 
with oil (ten grains to one fluidounce), it is one of the very best 
remedies that can be used, relieving pain by its anesthetic proper- 
ties and at the same time lessening suppuration and facilitating 
cicatrization. 

The use of phenol as a local anesthetic has been entirely done 
away with by the discovery of the powers of cocaine. 

So far as we know, the first to suggest and employ deep injec- 
tions of carbolic acid as a means of combating deep-seated inflamma- 
tion* was J. A. Eames; but the method has been especially studied 
and practised by Hucter with asserted extraordinary success in 
glandular swellings and inflammations, phlegmons of all grades and 
characters, erysipelas, poisoned wounds, inflamed bursa-, hydrocele, 
and even in bone disease. 

The practice has been followed with satisfaction by Aufrecht in 
erysipelas, by Senator, Mader, and Kunze in acute and subacute 
rheumatism, by Hagen in several diverse inflammations, and by I. 
Schmidt in chronic synovitis. These injections have been practised 
by Hagen with asserted excellent results in severe angina (the 
injections were in the neighborhood of the second tracheal cartilage): 
by .Moses K. Taylor in one hundred and fifty cases of buboes and other 
enlarged glands, with uniform success: by Mutschler with success in 
anthrax. The total evidence seems to show that this method of 
treatment is both safe and effective. f 

* In dispensing this, if capsules be used, the two ingredients should be thoroughly mixed 
before putting in; if an emulsion be employed, the bottle should be stood on its cork or laid upon 
its side, to prevent permanent separation of the bismuth. 

t As this method is of surgical rather than medical interest the reader is referred for details 
either to the authors quoted, or to surgical treatises. 



070 EXTRANEOUS REMEDIES 

Toxicology. — Probably on account of the ease with which it 
is procured and the quickness of its action, phenol is among the most 
popular of poisons. According to Harris, out of five hundred and 
forty-nine fatal cases of poisoning with it which occurred in England 
during four years four hundred and twenty were suicidal. 

The symptoms usually appear in a very short time after the 
ingestion of the poison, and when the dose has been sufficient may 
develop so rapidly that death occurs within three minutes. Usually 
the patient lives from one to ten hours, and life has been protracted 
for sixty hours.* 

Taylor records a case in which about an ounce is supposed to have been ingested, 
and in which the man fell in a stupor within ten seconds after taking the fatal 
draught, two minutes afterwards was totally unconscious, pulseless, with irregular 
distant gasping respirations, and in less than a minute later was dead, apparently 
from cardiac paralysis, since the impulse of the heart was entirely lost before the 
cessation of respiration. 

Usually, but not always, a burning pain is first felt in the mouth, 
oesophagus, and stomach, followed in a few minutes by nausea, 
cold sweats, and stupor deepening rapidly into insensibility and 
collapse. During the period of insensibility, complete abolition of 
reflex movements and anesthesia of the mucous membranes have 
sometimes been noted: f indeed, it is scarcely doubtful that in all 
cases both sensibility and reflex movements are profoundly affected. 
Convulsions are only exceptionally present. The symptoms of col- 
lapse are usually well developed, and the pulse is generally feeble 
and very frequent, but has been recorded as being reduced to from 
40 to 50 per minute (Hainworth). Hemoglobinuria has been noted. 
Dyspncea is often extreme; the respirations may be stertorous, are 
usually very rapid, and, in the advanced stages, shallow. In very 
rapid cases they are irregular and suspended at intervals. Total 
temporary amaurosis, with contraction of the pupil, has been noted. J 

In some cases of carbolic acid poisoning a great amendment has 
occurred and consciousness been restored, but after some hours 
rather sudden fatal collapse has come on. The minimum fatal dose 
of carbolic acid is not known; but half an ounce has several times 
caused death, § and a little over a drachm is reported to have killed 
a man sixty-four years old (Swain); in a case of puerperal metro- 
peritonitis fifty drops contributed towards the fatal result (A. D. 
L. Napier). 

The free external use of phenol is by no means devoid of danger; 
Falckson, after two hours' exposure to phenol spray, recovered from 
his urine thirty grains of phenol, and he describes a marasmus or 
chronic poisoning resulting from the surgical use of the remedy. 

* Case, Sydenham Soc. Y ear-Book, 1871-72, 446; amount taken, one and a half ounces of the 
commercial acid. 

t Case, Journ. de Pharm. et de Chim., Dec. 1871. 

t Case, Berlin. Klin. Wochenschr., xix. 748. 

§ Med. Times and Gazette, 1870, ii. 474: Phila. Med. and Surg. Rep., Jan. 1870; Lancet, 1878, 
ii. 510. 



DISINFECTANTS 671 

The symptoms are said fco be headache, loss of appetite, bronchial 
irritation, which finally may become very severe, severe pains in 
the region of the kidney, recurring vomiting, pruritus, or various 
paresthesia 1 , and loss of power in the legs. (See also Wallace.) 

A single vaginal injection has produced very severe constitutional results, 
K. Kohler reports the case of two journeymen joiners, suffering from scabies, who 
applied externally each about a half-ounce of phenol, in watery solution. One 
of them was found dead. His fellow, who suffered from unconsciousness and drunken 
delirium ending in unquiet sleep, after his recovery stated that directly after rubbing 
himself with the solution he had giddiness, that seven or eight minutes later bis 
companion complained of burning, but that of what took place after this he knew 
nothing.* 

It is scarcely necessary to refer in detail to cases in which seri- 
ous results have followed the surgical use of phenol. f A very severe 
case of poisoning is recorded, in an infant, produced by the use of 
carbolized cotton wool. The local application of phenol has in a 
number of instances been followed by local gangrene, which A. 
Frankenburger has attributed to thrombosis, but Harrington believes 
has been due to a direct chemical action. 

The post-mortem lesions of phenol-poisoning are usually well 
marked. If the acid has been ingested in a concentrated form, white, 
hardened spots are found upon the mucous membrane of the mouth, 
oesophagus, stomach, and even intestines. They are, of course, due 
to the local action of the poison, and are sometimes blackish in the 
centre, or even blackish throughout, and very generally are sur- 
rounded by a red inflammatory zone. The liver, spleen, kidneys, 
and indeed all the organs, are found filled with dark, imperfectly 
coagulated blood, such as is habitually found after death from 
asphyxia. Neumann found in experimental poisoning in the lower 
animals constantly fatty degenerations, but Salkowski was unable 
to obtain such changes and, according to Husemann, the fatty degen- 
eration of the liver and kidneys is neither in man nor in animals a 
constant characteristic phenomenon of phenol-poisoning. Reuder 
found the renal epithelium degenerated in a man who had been 
fatally poisoned by the drug. 

The diagnosis of phenol-poisoning during life ought in most cases 
to be practicable; for, although the symptoms simulate some forms 
of apoplexy too closely for the diagnosis to be made from them, 
very generally the odor of the drug can be perceived about the person 
of the victim, and close examination of the mouth will nearly always 
reveal traces of the local action of the phenol, in the form of white, 
hardened,, or corrugated patches of mucous membrane. Either these 
or a blackish urine in conjunction with the symptoms are diagnostic. 
After death a strong odor of phenol can almost always be perceived 
when the body is opened, and the mucous membrane of the stomach 

* For other fatal cases consult Bull. Therap., lxxv. 285. 

t Consult British Medical Journal, March 1, 1873, — death from absorption by a wound four 
inches long; New York Medical Gazette, April, 1871; British Medical Journal, 18R8, 220, — two 
fatal cases; Med. Times and Gaz., 1878, ii. 461; Wiener Med. Wochenschrift, 1879, xxix. 1233. 



672 EXTRANEOUS REMEDIES 

affords very reliable evidence as to the cause of death. According 
to A. Hiller, the urine of phenol-poisoning as first passed varies from 
a clear yellow to a golden yellow, and upon standing in the air becomes 
dark olive and finally often blackish-green. Sometimes it is grass- 
green, but it may appear to be normal. This phenol urine, if treated 
with nitric acid and afterwards with potassium hydroxide, becomes, 
after a certain degree of concentration, blood-red or brown-red, 
changing through pea-green to violet. Phenol mixed with urine 
does not answer this test. The absence of phenol urine proves that 
the case is not one of poisoning. Baumann and Hueter declare that 
the earliest symptom of the poisoning is the disappearance of the 
sulphates from the urine. 

In the treatment of a case of phenol-poisoning emetics are generally 
useless, owing to the existing paralysis of the stomach, and the 
stomach-pump must be employed to empty the viscus. As anti- 
dotes to phenol various substances have been suggested, but are 
of doubtful value. Those which have attracted most attention 
are the sulphates and alcohol. It is very doubtful if the sulphates 
have any antidotal action but as they are at least harmless they 
should be employed. Alcohol is in no sense antidotal to phenol. 
In external burns it acts favorably because being a good solvent for 
phenol it washes the irritant away (Ascher and Clarke and Brown) ; 
in internal poisoning it may easily do harm' by aiding absorption of 
the poison. It may, however, be useful to wash out the stomach 
providing no residue is left behind. 

The practical treatment of phenol-poisoning should be lavage 
of the stomach with ten-per-cent. solution of alcohol (or whisky), 
followed by administration of magnesium sulphate, the use of stimu- 
lants as indicated and the treatment of the subsequent gastritis with 
demulcent remedies. 

Alkalies in excess Lave been specially commended by Husemann, who 
employs saecharated lime.* In 1878 Baumann and Hueter stated that if a 
dilute sulphuric acid or a soluble sulphate be given freely to the animal 
poisoned with carbolic acid the latter will be converted into a harmless 
phenol-sulphonic acid.f 

David Cerna and also Cafawy believed to have obtained favorable results in 
experimental poisoning. Their technique was called in question, however, by 
Tauber, who found in a number of experiments that neither the sodium sulphate 
nor the pyrosulphate evinced any antidotal influence in the poisoned rabbits. He 
further concluded, as the result of his experiments, that the sodium sulphite 
is of distinctly antidotal value. Sollmann and Brown likewise were unable to 
demonstrate any antidotal action of sodium sulphate. 

On the other hand, Jos. Szydlowsky saved a pulseless and apparently dying 
child, ten hours after the ingestion of phenol, by hypodermic injections of ether 
and the administration of dilute sulphuric acid and sodium sulphate. In a careful 

* Dissolve sixteen parts of sugar in forty parts of distilled water, and add five parts of caustic 
lime; digest for three days, stirring from time to time, filter, and evaporate to dryness. The 
product thus obtained dissolves easily in water. 

t For a study of sulphocarbolic acid, see La Tribune Med., July, 1884, 328. M. F. Vigier 
affirms that, while not poisonous to the higher animals, it is an active antiferment. M. Rabuteau 
(Compt.-Rend. Soc. Biol., 1882 iii. 42) finds that the acid is simply a feeble purgative. 



DISINFECTANTS G73 

Btudy free from the objections urged against some of the earlier investigators I'io 
Mar fori concluded that the soluble sulphates, given either through the gastro- 
intestinal canal or injected hypodermically, arc distinctly antidotal to carbolic 
aoid, but that there is a limitation to their power, so that if too much phenol has 
been taken the sulphates will prove of no value. 

Maberly has recently suggested iodine as a chemical antidote to phenol. 

Phenyl Salicylate. — Salol. — This is a white, nearly tasteless, 
insoluble crystalline powder, which is prepared by replacing one atom 
of the hydrogen of salicylic acid by phenol. It is decomposed by 
alkalies, and. consequently, is broken up in the intestinal tract, 
yielding about thirty-six per cent, of phenol, and sixty-four per cent. 
id" salicylic acid. Although less powerful as a poison than are its 
united ingredients, probably because it is broken up slowly in the 
intestines and escapes with the feces to some extent unchanged, 
salol is capable of producing concurrent symptoms of salicylic-acid 
and of phenol-poisoning. Kumagawa has found that it increases 
nitrogenous elimination. 

Salol was originally introduced into medicine by Sahli as an 
antirheumatic, but is at present employed solely as an intestinal 
disinfectant. According to Lesnik it has practically no influence 
upon ordinary bacteria. Its effectiveness as an intestinal antiseptic 
evidently depends upon phenol and salicylic acid, which are liberated 
by its decomposition. In the experiments of Kumagawa on animals, 
large doses of salol failed to lessen the elimination of indican by the 
urine or the number of bacteria in the intestines; nevertheless, in 
typhoid fever, intestinal indigestion, and allied complaints, salol 
may be considered as probably the most effective of our intestinal 
antiseptics. 

Externally salol has been used as an antiseptic dressing, but is 
of very little value. 

One hundred grains a day of salol have frequently been given 
without serious effect, probably because the larger proportion of 
the salol has escaped unchanged with the feces. Hesselbach claims 
that the long-continued use of salol is dangerous when the kidneys 
are diseased, on account of the irritating influence of phenol on these 
organs. The ordinary dose is from ten to fifteen grains (0.6-1 Gm.), 
as an intestinal disinfectant, administered in capsules one hour 
after meals. 

Phenol-Sulphonic Acid. — Both the sodium and zinc salts of sulpho-carbolic 
acid are official in the U. S. Pharmacopoeia. (Sodii Phenolsulphonas, Zinci Phenol- 
sulphonas.) The sulphocarbolates were introduced some years ago as intestinal 
antiseptics, for which purpose it was evidently expected they would possess the 
antiseptic virtues of carbolic acid and the innocuousness of the sulphocarbolates. 
It has been shown, however, by Withers that they are not possessed of any direct 
antiseptic power. More recently it has been claimed for them that they are decom- 
posed in the intestinal tract with the liberation of carbolic acid, but we know of no 
experimental or scientific evidence tending to show the truth of this belief, and their 
value is extremely doubtful. 

43 



674 EXTRANEOUS REMEDIES 

CREOSOTE. 

This substance is defined by the U. S. Pharmacopoeia to be a 
mixture of phenols, chiefly guaiacol and creosol, obtained during the 
distillation of wood-tar, preferably of that derived from the beech 
(Fagus sylvatica Linne). It is stated that the beech-wood creosote 
ranges in the amount of guaiacol from sixty to ninety per cent. 
It has been much confused with phenol, and for many years most 
of the creosote of the drug-stores was an impure carbolic acid. For 
the tests distinguishing creosote from carbolic acid, see United States 
Dispensatory. The creosote of commerce is an oleaginous liquid, 
colorless, or brownish or reddish, having a caustic taste and a pene- 
trating disagreeable odor, which while resembling that of phenol 
markedly differs from it in being more smoky. It requires 140 times 
its weight of water to dissolve it but is freely soluble in alcohol. 

Creosote Carbonate or Creosotal is a mixture of the phenol-car- 
bonates of the several constituents of creosote, containing about 
ninety per cent, of creosote. It is a thick, oleaginous, pale yellow, 
almost tasteless liquid, insoluble in water, soluble in fatty substances. 
Although unofficial it has been largely employed. 

Official Preparations: 

Creosotum 5 to 15 minims (0.3-1 C.c). 

Aqua Creosoti (1 per cent.) \ to 1 fluidrachm (2-4 C.c). 

Physiological Action. — The physiological effects of creosote 
have never been carefully and thoroughly studied. It certainly 
rivals phenol in its antiseptic power. 

Sternberg has found that a 1 : 200 solution of creosote destroyed the pus cocci 
in two hours' exposure. Bucholz ranks creosote as superior to phenol, but inferior 
to salicylic acid. 

Creosote is, when applied locally, a paralyzant to the nerves, 
and probably to all higher tissues; indeed, it has been generally 
believed to be physiologically almost identical with carbolic acid. 
It differs, however, greatly from carbolic acid in its toxicity and in 
its therapeutic usefulness. 

The symptoms of creosote-poisoning are similar to those caused 
by phenol, — namely, burning in the gullet and stomach, vertigo, 
faintness, unconsciousness, collapse, blackish urine, stertorous breath- 
ing, and great cardiac depression. Zawadzki reports a death alleged 
to have been produced by three six-drop doses of creosote, taken in 
the twenty-four hours. 

Freudenthal * reports the case of a woman who took six hundred drops of creo- 
sote in a very short time, the ingestion being followed almost immediately by 
unconsciousness, with intense trismus, contracted, immobile pupils, and general 

* For other cases of creosote-poisoning, see Miiller (Wilriemb. Corresputidenz-Blatt, 1869), 
T. Stevenson (Gvy's Hosp. Rep., 1875, xx. 144), Piirckhauer (Friedreich's Blatter j. Gericlit. Med., 
1883,430), F. Grinell (Med. News, xl. 345), Manouvriez (.S'oc. Med.-Legale de France, vii. 108), and 
Faisans (Bull. Med. Soc. Med. d'H6p. de Paris, 1896). 



DISINFECTANTS 875 

cyan. )ms, hut in which recovery occurred without, the administ nil inn of remedies 
lie further states that subsequently the same patient, by increasing the doae of 
creosote, was able to lake five hundred drops daily without ill effect. 

The absorption and elimination of creosote are very rapid. 

Saillet, within the nine hours following the administration of eight centigrammes, 
obtained from the urine forty-eight milligrammes; alter sixteen centigrammes, 
one hundred and eleven milligrammes; and it would appear that about two-thirds 
of the dose escapes from the body through the kidneys in the time mentioned. 
Imbert recovered one gramme of guaiacol from the urine after the hyr>odermie 
injection of two grammes; after two grammes of a mixture of guaiacol and creosol, 
sixty centigrammes; and so on: so that it would appear that a portion of the creo- 
sote is destroyed in the body. This conclusion is, however, rendered doubtful by 
the fact that the creosote escapes through other channels than the kidneys. 

Creosote has been found abundant in the sputa of phthisical 
patients, and, indeed, Catillon affirms that it is chiefly thrown off 
through the lungs. It occurs in the urine probably in part as oxidized 
educts, but chiefly as creosol and guaiacol sulphates: so that, as 
shown by Hobert A. Hare, sulphuric acid and the soluble sulphates 
are antidotal to it.* 

Therapeutics. — The most important use of creosote is as a 
stimulant expectorant in chronic bronchitis and phthisis. The old 
theory that creosote did good in phthisis by virtue of its antiseptic 
action is, in the light of recent research, hardly tenable. 

Any such action must be purely local, — i.e., due to creosote excreted in the 
lung, — since F. Holscher and Richard Seifert found that in young rabbits and 
dogs to which guaiacol has been freely given the serum of the blood was at no time 
capable of checking the development of bacilli in agar-agar. Schill and Fischer 
((pioted by Sternberg) found that a one-per-cent. solution of creosote failed to 
destroy the tubercle bacilli in the sputum after two hour's exposure. It seems to 
be established that creosote is largely eliminated with the sputa; but Bogdonovitch 
and other clinicians or experimenters have found the bacilli abundant and active 
in the sputa of phthisical persons taking the remedy. Brissonet, Holscher and 
Seifert present evidence to show that guaiacol neutralizes in the blood those poison- 
ous products of bacillary growth which are the cause of the fever, sweating, dis- 
ordered digestion, etc., of the phthisical patients; in other words, that creosote 
acts chemically in the blood. At present this seems to be nothing more than an 
ingenious theory. 

On account of its local action as a nerve paralyzant, creosote is 
frequently employed with great advantage in nausea, vomiting, or 
diarrhaa dependent upon excessive irritability, without acute inflam- 
mation of the gastric or intestinal mucous membrane; it has thus 
been successfully used in the vomiting of pregnancy or of hysteria, 
in cholera morbus, cholera infantum, lienteric diarrhoea, typhoid fever, 

* Imbert finds that the proportion of creosote eliminated diminishes with the increase of Hie 
dose. Thus, after an enema of one gramme, fifty-four to sixty percent, was found in the urine; 
after two grammes, forty-eight per cent.; after four grammes, thirty per cent. When four grammes 
were administered, the expectorations snowed its presence for twelve hours. After a subcutaneous 
injection, Imbert was not able to recover from the excretions more of the creosote than after it 
had been given by enema. Although there were severe persistent pain and swelling, no suppuration 
mi sloughing ever followed these injections. Imbert also found thai the elimination ceased at the 
end of twelve hours after large a^ well as small doses (Bull. Gen. Tin rap., 1892, exxii.). For methods 
of finding creosote iu the urine, see also Bull. Gin. Thirap., May 18 l J2. 



G76 EXTRANEOUS REMEDIES 

and even in dysentery* When in these cases there is a tendency to 
fermentation of the contents of the stomach or bowels, creosote is 
especially valuable, and may often be combined advantageously 
with an alkali or chalk. Whether it is in these affections superior 
to phenol is doubtful. 

Externally, creosote has been employed for exactly the same 
purposes as has phenol. The skin diseases to the treatment of which 
creosote has been supposed to be best suited are those of a scaly 
character. In burns its efficacy has been insisted on, especially when 
there is excess of suppuration or of fungous granulations. Also in 
chilblains it is stated to be a useful application. Mixed with four 
parts of lard, it is said to have proved very serviceable in erysipelas. 
When applied to wounds it acts as a hemostatic, stopping the capil- 
lary hemorrhage, but it possesses no power to arrest the bleeding 
from large vessels. Accordingly, creosote-water has been applied 
locally in menorrhayia, and to arrest uterine hemorrhage and the bleed- 
ing from leech-bites. Wherever there are foul ulcers, gangrenous 
surfaces, or inflamed serous, mucous, or glandular tissues giving rise 
to fetid discharges creosote may be substituted for phenol; as 
examples may be mentioned fetid leucorrhoea, puerperal metritis, fetid 
otorrhaa, putrid or diphtheritic sore throat, chronic empyema, and 
chronic fistula. The strength of the application may vary from that 
of pure creosote to a one-per-cent. solution. 

The ordinary dose of creosote is from three to five minims (0.2-0.3 
C.c.) three to six times a day, in chronic cases increased to one or 
even two fluidrachms a day, as borne by the patient. Creosote in 
capsules should be taken upon a full stomach. Large doses of it 
should always be freely diluted with water and glycerin, or milk 
or cod-liver or other oils, to avoid local irritation. The hypodermic 
use of creosote, as practised by Perom in phthisis (ten-per-cent. 
solution in oil of sweet almonds), is not to be favored. 

Creosote carbonate is claimed to have the advantages of being 
less disagreeable to the taste and better tolerated by the digestive 
apparatus. It is decomposed in the system, and is capable of pro- 
ducing blackish urine. It is, however, much less poisonous than is 
creosote, and probably when large doses are exhibited escapes in 
part from the alimentary canal. Fifteen drachms of it are asserted 
to have been given in a day without unpleasant symptoms; and it 
has been used hypodermically after warming, so as to increase its 
fluidity. It may be given in capsules, or preferably in emulsion in 
milk. 

Guaiacol. — Methyl Pyrocatechin. — Guaiacol is a phenoloid body, 
constituting from sixty to ninety per cent, of creosote, from which 
it may be obtained by fractional distillation, or it may be prepared 
synthetically. It occurs as a colorless crystalline solid, and also as 
a syrupy liquid of an agreeable aromatic odor. It is soluble in 
fifty-three parts of water and very freely in alcohol and ether. 



DISINFECTANTS (177 

Guaiacol Carbonate (Duolal) occurs as a neutral, white, almost 

tasteless and odorless crystalline powder, insoluble in water, soluble 
in forty-eight parts of alcohol. 

Official Preparations : 

Guaiacol 5 to 10 minima (O.li-O.G Co.). 

Quaiacolia Carbonas 10 to 20 grains (0.6-1.2 Gin.). 

Guaiacol acts in concentrated form as an irritant and as a germi- 
eiile. As originally pointed out by Andr6, it has also distinct- anes- 
thetic properties which are not, however, sufficiently pronounced 
to make the drug useful as a local anesthetic. In the experiments of 
J. Kuprianow guaiacol was found to be distinctly inferior to creosote 
and to phenol in general germicidal iniluence, but to be especially 
poisonous to the tubercle bacillus. 

Guaiacol is absorbed and eliminated with great rapidity. Linossier 
and Lannois were able to recognize it in urine passed fifteen minutes 
after its local application to the skin, and to obtain from the urine 
of the next twenty-four hours nearly half of the whole amount used. 
In the experiments of Eschle the greatest part of the ingested guaiacol 
or guaiacol carbonate was eliminated within twenty-four hours, 
about half of it going out with the urine in combination with sul- 
phuric acid; of the remainder the greater part was eliminated as 
glycuronic acid. 

The general physiological action of guaiacol has not been studied 
to any extent, but appears to be similar to but less powerful than 
that of phenol. 

Therapeutics. — The suggestion of Guinard that guaiacol be 
used externally as an antipyretic in phthisis has led to its trial in 
•pneumonia, typhoid fever, and other acute diseases. The thoroughly 
cleansed skin of the abdomen or chest is painted by means of a camel's- 
hair brush with from twenty to fifty minims, and an impermeable 
dressing applied to prevent evaporation. The fall of temperature 
produced by the guaiacol used in the manner described follows with 
great certainty, but has too often been excessive and accompanied 
by pronounced collapse to allow the drug to be considered a practical 
antipyretic. 

Guaiacol is used as a substitute for creosote in tubercular and 
other chronic catarrhs, and is very effective. It is also used locally in 
lupus and other forms of surgical tuberculosis. Thus, in tuberculosis 
of the bladder, and even in chronic cystitis, from fifteen to thirty 
minims of a five- to twenty-per-cent. solution in sterilized olive oil 
may be injected daily into the bladder. Inhalations of the aqueous 
solution (1:600) have been considerably used in pulmonic tuberculosis, 
but it is not probable they have any effect except upon the catarrh 
of the mucous membranes. 

Guaiacol carbonate is much used as a substitute for guaiacol on 
account of its freedom from taste and of its being less irritant. It is, 
however, much less active than is guaiacol, both as a local and general 



678 EXTRANEOUS REMEDIES 

agent. In the experiments of W. Hesse it was found to be so slightly 
poisonous that it seems probable that when it is taken internally 
much of it passes through the alimentary canal unabsorbed. 

Orthogtjaiacol-sttlphonic Acid, or Theocol, occurs as a white, micro-crys- 
talline, odorless, permanent powder, of a faint bitter saline taste, soluble in water 
and dilute alcohol. It has a powerful reducing action on silver salts and ferric 
compounds, and at once decolorizes permanganate solution. Hatch claims it to 
be of great value in bronchitis, pneumonia, phthisis, and all forms of infective 
inflammations of the lungs. He thinks it attacks the bacilli. 

CRESOL. 

Homologous with phenol are the three isomeric compounds, 
orthocresol, metacresol, and paracresol, a mixture of which is recog- 
nized by the U. S. Pharmacopoeia under the name of cresol. This is 
a colorless or straw-colored refractive liquid with a phenol-like odor, 
soluble in sixty parts of water and miscible in all proportions with 
alcohol and glycerin. It is a later product of the fractional distilla- 
tion of coal-tar, and is practically the substance which has long been 
known in commerce as cresylol, or cresylic Acid. 

Cresol is soluble in sixty parts of water at 25° C, but is rendered 
more soluble by the presence of soap. This is the explanation of the 
complete miscibility with water of the official compound solution 
of cresol, as well as the various proprietary preparations of cresol. 
The addition of lime salts and the use of hard water in making solu- 
tions of compound solution of cresol, on account of the insolubility 
of the lime soaps, produces a turbidity of the solution, which, 
however, it is claimed does not interfere with its germicidal activity. 

Official Preparations: 

Cresol 1 to 2 minims (0.06-0.12 C.c). 

Liquor Cresolis Compositus (50 per cent.) . .External use. 

Although it seems established that cresol is a more active germi- 
cide than phenol, what knowledge we have of its physiological activi- 
ties is derived so largely from studies of proprietary preparations, 
whose real combination is a matter of doubt, and is so imperfect that 
positive conclusions as to its exact value must be drawn with caution 
especially as the three cresols differ somewhat in their properties. 

Henri Delplanque affirms that cresol is stronger than phenol as a germicide 
and has only one-fourth of its toxicity. Frankel found that a 0.3 per-cent. solu- 
tion of cresol destroyed the staphylococcus aureus, and the streptococcus ery- 
sipelatus in five minutes, while a two-per-cent. solution of phenol required fifteen 
minutes to accomplish the same result. The statement of Frankel that the com- 
pound of cresol with sulphuric acid is soluble in water, scarcely irritant, and more 
powerful as a disinfectant than is phenol, seems to us highly improbable. Weiss 
found that a three-fourths-per-cent. solution of lysol * destroyed various bacteria 
(pus cocci, typhoid bacillus, etc.) in five minutes, and the anthrax spores in one hour. 
According to the results of Burgess, however, lysol is not greatly superior to phenol. 

* Lysol appears to correspond closely in composition and strength to the official compound 
solution of cresol. 



DISINFECTANTS 679 

That oresol is poisonous has been proven by Faust, and Fries has oolleoted 
thirty-eight cases of lysol-poisoning, of which eleven were from external use, with 

lour deaths; twenty-seven from internal use with thirteen deaths. He places l he 
toxic dose at about I 5 C.e. for children, and 10-12 C.e. for adults. Bluiuciii lial 
states i hat about 100 cases of lysol-poisoning occur annually in Berlin. Maass 
affirms that lysol is eight times less poisonous than is phenol, and one-half as poison- 
ous as creolin. Tollcns has shown that although paraeresol is slightly less toxic 
than phenol commercial cresol is fully as poisonous if not more so than phenol, 
whether in aqueous or saponaceous solution. It is certainly less caustic in 
concentrated solution than is phenol. 

The symptoms of cresol-poisoning arc nausea and vomiting, 
general depression with stupor, fall'of the bodily temperature, smoky, 
albuminous urine, ending in fatal cases in coma and collapse. 

The compound solution of cresol offers a valuable substitute 
lor phenol as a germicide in all purposes in which the older prepara- 
tion is useful. It has the advantages of greater power, less irrita- 
tion, ami lower toxicity. Its saponaceous character makes it 
especially valuable in cleansing the skin or the surgeon's hands. 
Although its extremely unpleasant taste and odor lessens its value 
in intestinal putrefaction and diarrhoeas, cresol has been recommended 
by Maass and Vondergoldz. 

Creolin is a soluble preparation, containing, according to Pfreuger, 2.7 per 
cent, of phenols, mostly cresol, suspended by means of resin soap. It has been 
assorted that creolin is not poisonous, Jessner stating that he had given one hundred 
and twenty grains (7.77 Gm.) to a man without production of distinct symptoms. 
It is almost certain, however, that its apparent lack of toxicity depends upon its 
non-absorption, due to insolubility; and human poisoning has been caused by it. 

Bitter has seen restlessness, anxiety, nausea, amblyopia, and a tendency to 
syncope, with a peculiar strong taste of tea or smoke, produced by the drug. The 
urine in some of his cases was dark and highly albuminous, acute nephritis having 
evidently set in. Fliesburg details a case of a three-weeks '-old babe who was killed 
by thirty drops of undiluted creolin, the chief symptom being those of violent 
irritation of the mouth and upper respiratory and digestive tracts. Death occurred 
chiefly through inflammation of the glottis. 

Eisenberg asserts that a three-per-cent. solution of creolin will kill anthrax 
spores in forty-eight hours, but on the other hand both Esmark and Van Ermen- 
gen failed to kill the anthrax spores with a ten-per-cent. solution after exposure 
for thirteen days. According to Burgess, a twenty-per-cent. solution of creolin 
destroyed the bacillus coli communis in five minutes, being equivalent to 
2.5-per-cent. solution of phenol. 

NAPHTHALENE. 

Naphthalene {Naphtalin) is a hydrocarbon obtained by the 
fractional distillation of coal-tar, or sometimes by the dry distilla- 
tion of organic bodies. It is a white, shining, crystalline substance, 
fusible at 176° F., insoluble in water, but soluble in alcohol, chloro- 
form, and ether. It is poisonous to the lower forms of life, and under 
the name of tar camphor has largely supplanted true camphor as a 
means of preventing the deposition by moths of eggs in woollen 
clothing, and the destruction by insects in natural history museums, 
etc. In internal medicine it was some years ago brought forward 



680 EXTRANEOUS REMEDIES 

by Dupasquier as an expectorant especially valuable in chronic 
bronchitis with a large amount of secretion. It has also been used 
with asserted excellent results as a tceniacide, and as a vermifuge in 
cases of seat-worms, when it should be given by injection, from fifteen 
grains to half a drachm in two or three ounces of olive oil. First 
employed by Rossbach, of Jena, in intestinal catarrh, it has been 
largely given in all forms of intestinal inflammation and in typhoid 
fever. It has also been used externally as an antiseptic dressing, and 
as a local application in various skin diseases. It has certainly proved 
effective in many cases, but has been supplanted by naphthol, which 
is similar to it in action and probably more effective. The ordinary 
dose is from two to eight grains (0.12-0.5 Gm.), but as much as 
eighty grains (5.5 Gm.) per day are said to have been given with 
good results. It is best administered as a powder in capsules. 

BETANAPHTHOL. 

Naphhtol is a phenol which is present in small quantities in coal- 
tar, but is usually prepared artificially by heating naphthalene with 
sulphuric acid and fusing the resulting naphthalin-sulphonic acids 
with alkaline hydrates. There are two naphthols, alpha and beta, 
of which betanaphtol is official. It occurs as colorless or pale buff 
crystalline laminae, or as a white or yellowish-white crystalline powder, 
of a pungent but not persistent taste, and a faint odor suggesting 
phenol. It is permanent in the air, very slightly soluble in water, 
very freely soluble in alcohol. 

Therapeutics. — Betanaphthol was introduced by Bouchard 
and Maximovitch into practical medicine as a germicide which might 
be used on or within the human body for the purpose of inhibiting 
the growth of disease-germs. It appears to be of only second rank 
as a germicide, but to have value on account of being nearly free 
from toxic powers in relation to the higher animals. 

Experimenters are somewhat at variance in regard to the exact germicidal 
power of betanaphthol. According to Bouchard and Maximovitch, in the labora- 
tory 1 to 3000 will kill some pathogenetic germs and greatly retard the growth of 
the bacilli of typhoid fever and of tuberculosis, while about three grains per quart 
will arrest putrefaction. The experiments of Surveyor and Harley, however, indi- 
cate that naphthol is less active as a germicide than is bismuth subnitrate. Bou- 
chard and Maximovitch, in contrasting experiments, found that mercuric iodide is 
six times more antiseptic than betanaphthol, but that phenol is five times less anti- 
septic, and creosote four times less antiseptic. Weeks found that 1 : 10 solution of 
betanaphthol in either destroyed the staphylococcus pyogenes in thirty seconds. 
The toxic dose of betanaphthol was found to be 3.8 grains per kilo of the animal, 
making it two hundred and fifty-three times less poisonous than mercuric iodide. 
At this rate the poisonous dose for an ordinary man would be between three and 
four thousand grains. In the animals killed by it, death took place through an 
arrest of respiration, the heart retaining its activity. 

In experiments made to determine whether digestion would be 
seriously interfered with by betanaphthol, Clarke found that it has 



DISINFECTANTS 681 

a very distinct retarding influence on the artificial digestion of egg 
albumin by peptic Quids, a very slight effect on the artificial digestion 
of milk by tbe same, and no effect at all on pancreatic digestion of 
milk or albumin, nor on the conversion of starch into sugar. 

Externally, betanaphthol was first used in L881 by Kaposi, of 
Vienna, who found it to be, when in solution in oil or alcohol, mark- 
edly irritating to the skin, 1 part to 100 distinctly affecting cczcniatous 
eruptions, and 1 to 1J parts per 100 being sufficient to provoke urti- 
caria on a healthy skin. In the form of soap, containing 2 parts per 
100, Kaposi found it useful in prurigo, ichthyosis, herpes, and favus, 
obtaining in many cases the best results by alternating this soap 
with a sulphur soap, and avoiding in this way a cumulation in the 
system which he believed was possible by the absorption of the drug. 
The practice of Kaposi was followed by numerous dermatologists 
with success, and led to the use of the remedy locally in inflammation 
of the mucous membranes, such as conjunctivitis, chronic laryngitis, 
otitis, etc. 

Bouchard introduced the internal use of the drug for the purposes 
of disinfecting pathological cavities, and for intestinal antisepsis, 
especially in typhoid fever. Following Bouchard, a large number of 
clinicians have reported excellent results from the administration of 
the drug in typhoid fever; it is affirmed that it lessens the diarrhoea 
and other local abdominal symptoms both in adults and children. 
The remedy has also come into use in cases of dilatation of the stomach, 
intestinal dyspepsia, diarrhoea, or dysentery, when it is desired to check 
fermentative changes in the alimentary canal without producing the 
astringent or sedative effects of bismuth salts. The slow injection 
into the trachea, drop by drop, during a half-hour, of two hundred 
to three hundred cubic centimetres of its solution (1 to 1000) is 
affirmed by Pignol to be a useful procedure in pneumonia. Teissier 
has given it intravenously; others have exhibited it by the mouth 
in epidemic influenza and low fevers for the relief of albuminuria; 
but these uses of it are of doubtful value. Larger doses than from 
three to four grains (0.20-0.25 Gm.), given in capsules every two 
hours, are likely to disturb the stomach. 

Betol of Sahli, or Naphthalol of Kobert, is p-naphlhol ether salicylate, and occurs 
in small, white, resplendent, almost tasteless crystals, insoluble in water. It is a 
compound analogous to salol, but having the base of naphthol instead of phenol 
and yielding, in the intestinal juices, salicylic acid and naphthol. It contains ten 
per cent, less salicylic acid than does salol, and is of no value in rheumatism, but has 
been much vised as an intestinal antiseptic, and has been highly recommended 
by Kobert in gonorrhoea and other forms of cystitis. Dose, five to fifteen grains 
(0.3-1.0 Gm.). 

Menthol, or Oil of Peppermint Camphor, has obtained great 
notoriety as a local anesthetic, and, if freely rubbed upon a part, it 
undoubtedly will often relieve neuralgic pains when they are super- 
ficial and peripheral in their origin: its solution (2 to 10 grs. — f.^i 
water) is said also to be very effective in pruritus ani, chronic painful 



682 EXTRANEOUS REMEDIES 

eczemas, urticaria, etc. Its physiological action has been studied by 
Paolo Pellacani. In the frog it causes paralysis, first of the spinal 
centres and finally of the nerve-trunks. In the mammal both mobility 
and sensibility are depressed, the animal grows cold, and the respira- 
tion becomes slow and shallow. Small doses excite, larger paralyze 
the frog's heart. In the poisoned mammal there were very curious, 
unexplained rhythms of rise and fall of the blood-pressure. 

Goldscheider lias been led to the conclusion that the sensation of cold produced 
by the local application of menthol is due to a special influence exerted upon the 
special nerves of temperature by finding, — first, that after the appUcation of a 
solution of menthol in lanolin the local temperature is increased 2° C, although a 
marked sensation of cold lias been produced; and, secondly, that the cold is not 
due to evaporation, because covering the part to which the menthol is applied with 
a watch-glass does not affect the sensation. He also found that if the menthol 
ointment were applied to one side of the forehead, bodies which previously had 
caused the sensation of cold no longer did so, and that application of menthol pro- 
duced a sensation of warmth upon the elbow and the volar side of the wrist, posi- 
tions at which, according to Herzen, similar warm sensations are caused by pressure 
upon the nerve-trunks. I. Ioteyko found that the sensation of cold is preceded by 
loss of general sensibility, and that the maximum of cold and anesthesia correspond. 

S. A. Russell affirms that menthol has a remarkable power of 
controlling superficial inflammations. He asserts that an ethereal 
solution, of the strength of from ten to fifty per cent., two or three 
times a day by means of a camel's-hair pencil, will control boils, 
carbuncles, sujjerficial abscesses, etc. It is very largely employed, in 
conjunction with camphor, as a local application in rhinitis and 
laryngitis. Bishop recommends a solution containing ten per cent, 
of each drug; more commonly a one- to two-per-cent. solution in 
liquid petrolatum is used by atomization. 

THYMOL. 

Thymol is a phenol found in the oil of thyme * (Thymus vulgaris) 
and of some other plants. It occurs either as an uncrystallizable 
liquid or in white rhombic or acicular crystals. 

Official Preparations : 

Thymol 5 to 15 grains (0.3-1 Gm.). 

Thymolis Iodidum External use. 

Liquor Antisepticus f External use. 

Thymol has been urged as a substitute for carbolic acid by Volk- 
mann and Ranke, of Halle, but, although a powerful antiseptic, has 
not come largely into vogue. Its fragrant odor has proved a decided 
disadvantage, in summer at least, by attracting swarms of flies. 
It is not free from poisonous properties. 

* According to Cardeac and Meunier (Journ. Med. Vet. Zootech., 1890), the physiological 
actions of the oils of Thymus serpyllum and Thymus vulgaris are the same; they produce in animals 
dilated pupils, staggering gait, hallucinations, loss of sensibility, muscular relaxation, insomnia, 
trembling, contractures, exceedingly rapid respiration, and death, preceded by complete muscular 
relaxation and anesthesia. 

t A word concerning those two greatly overestimated preparations Liquor Antisepticus 
U.S. P. and Liquor Antisepticus alkalinus N.F. and their proprietary kin Listerine and Glycothy- 



DISINFECTANTS lis;} 

According to Sternberg ;i one-fourth-per-cent. solution of thymol is alcohol 
is equivalent in germicidal properties to one- and one-fourth-per-cent. Bolution of 

carbolic acid against the coccus of mouth septicemia. Huchol/, ranks thymol us 
about the same strength as salicylic acid. 

It has been used internally by Hal/, in doses of thirty grains a day, or less. 
In a few instance's nausea and vomiting were caused. There were abundant sweat- 
ing, singing in the ears, deafness, constriction in the forehead, reduction of tempera- 
ture, and frequently diarrhoea. The urine was dark greenish, yellowish-brown by 
transmitted light, free from albumin, becoming cloudy and grayish-white on the 
addition of the tincture of the chloride of iron. Violent delirium occurred several 
times, also marked collapse, and, in one case of typhoid fever, unconsciousness, 
with most alarming collapse. Hiilz concludes that the remedy is much less certain 
and more dangerous as an antipyretic than is salicylic acid. 

The possession of poisonous properties by thymol has been confirmed by the 
experiments of R. Kiissner. This observer found that when given to dogs and 
rabbits by the stomach the poison acts very slowly and feebly, on account of its 
slow absorption, but when injected into the circulation is produces death by failure 
of respiration. Post-mortem examination failed to detect fatty degeneration or 
other lesion in either the solid tissues or the blood. The continuous repeated exhibi- 
tion of small doses of thymol had no perceptible effect, except to interfere in some 
way with nutrition, so that the animals lost flesh. Kiissner has found that thymol 
has the power of dissolving the red blood-corpuscles. 

Thymol is eliminated through the kidneys partly as thymol itself, partly as 
thymo-hydrochinone united with sulphuric acid, partly as a chromogen, which is 
probably an oxidation product of thymol, and partly as some acid of unknown 
constitution (F. Blum). 

Thymol on account of its agreeable taste is largely employed as 
an antiseptic in diseased conditions of the mouth and throat. It is 
no longer used in diabetes as suggested by Kiissner; * nor as an intes- 
tinal antiseptic in typhoid fever as recommended by Martime and by 
F. P. Henry. It has been recommended by Fischer and others in 
pertussis. Thymol is also employed as an anthelmintic (see p. 646). 
Dose, fifteen to twenty grains (1-1.3 Gm.) in the twenty-four hours. 

RESORCINOL. 

Resorcinol (resorcin), pyrocatechin and hydroquinone, are three 
dioxybenzols, resembling each other very closely in physiological 
effects, but of which only resorcinol is used in medicine. This occurs 
in colorless, short, aromatic prisms or plates of an unpleasantly sweet, 
somewhat acrid taste, which on exposure to the air becomes reddish. 
It is soluble in half of its weight of water, also in alcohol, or ether, 
and in about twenty parts of fixed oil. 

Physiological Action. — Local Action. — Elimination. — Resorcinol 
is an active irritant, but is scarcely able to act as an escharotic. 
According to Joseph Schomacker, it is eliminated with the urine as a 
sulpho-acid, which on boiling with HC1 is decomposed, resorcinol 
being set free; after very large doses, free resorcinol may be found 
in the urine. The excretion is said to be completed in about seven 

moline may be in place here. The antiseptic power of any of these preparations is so extremely 
slight that they are practically worthless, except as more or less pleasant vehicles for mouth washes 
and gargles. 

* See Furbringer (Deutsches Archil) f. Klin. Med., xxi.). 



684 EXTRANEOUS REMEDIES 

hours. It is actively poisonous to the lower organisms, and, accord- 
ing to Martin Cohn and Andeer, a one-per-cent. solution of it is suffi- 
cient to arrest, for a long time, putrefactive changes in the urine, 
organic infusions, and even animal tissues. Piatt states, however, 
that it is distinctly inferior to phenol as an antiseptic. 

General Effects. — In doses of twenty to forty grains resorcinol 
causes flushing of the face, with giddiness, buzzing in the ears, and 
some quickening of the breathing and pulse, followed, after a time, 
by violent perspiration and sometimes depression of temperature. 

Andeer took about one hundred and fifty grains of resorcinol, dissolved in a 
pint of water, during fifteen minutes. After disturbance of the cerebration and of 
the special senses, he fell into a condition of collapse, with cold extremities, epilep- 
tiform convulsions with loss of consciousness, opisthotonos, and marked disturb- 
ance of the respiration. Consciousness did not return for five hours. Murrell records 
a case in which a woman took one hundred and twenty grains of resorcinol, and 
immediately felt giddy, had sensation of pins and needles all over her, and a few 
minutes later was insensible, with closed eyes, clenched hands, pallid, blanched 
lips, dry tongue, normal pupils, and insensible conjunctiva; the temperature was 
94° F.; the reflexes were entirely gone; the pulse was weak and thready. Jos. 
Loeffler reports the case of a woman, thirty-one years old, who, immediately after 
the injection into the stomach of two litres of a three-per-cent. solution of resorcinol, 
was seized with violent gastric pain, followed at once by unconsciousness, cyanotic 
face, and clonic contractions. In spite of the immediate removal, as far as possible, 
of the solution, the cyanosis became more intense, the unconsciousness and mus- 
cular relaxation complete, with, from time to time, active tremors; the pulse very 
small and frequent; the respiration completely arrested, with respiratory muscles 
in such a condition of tetanus as greatly to embarrass artificial respiration. Under 
the continued use of artificial respiration, however, recovery was finally secured. 
In several cases of children the washing out of the stomach with a three-per-cent. 
solution has been followed by collapse and death, and in one case hemoglobin was 
found in the urine. 

In the lower animals (Dujardin-Beaumetz) resorcinol causes tremors, loss of 
consciousness, and epileptiform convulsions, which, when the dose lias been suffi- 
ciently large, become more and more violent, until the increasing disturbance of 
breathing ends in respiratory arrest. During the spasms the temperature of the 
animal is distinctly elevated, but when there is quiet narcosis it may fall below 
normal. The urine becomes olive-green, deepening into blackish. 

Resorcinol resembles phenol in being a universal poison, but is 
less active. It probably affects the nerve-centres as does phenol, 
and has been shown by Beyer to be a direct cardiac paralyzant. 

Therapeutics. — Resorcinol is used almost solely as a topical 
remedy in diseases of the skin and mucous membranes. It has been 
highly recommended by Hoefer, Lichtheim, Janicke, Fliesburg, 
Baginsky,* and others in various acute and subacute gastric or intesti- 
nal inflammations, such as enteritis, gastric ulcer, and cholera infan- 
tum, but in our experience has not given satisfaction. In hay {ever, 
chronic otitis, gonorrhoea, leucorrhoza, and other mucous catarrhs, it 
may be applied locally in the solution of from one to fifteen-per- 
cent. The three- to five-per-cent solution has been largely used in 

* See Therap. Gas., ii. an<I iii., and Berliner Klinische Wochen., 1889, XXV). 






DISINFECTANTS 885 

Germany in washing out diseased stomachs, hut care is necessary to 
avoid poisoning. Ln chronic cystitis irrigation of the bladder with 
a three-per-cent. solution has been found effective. 

It is said to be valuable in the treatment of the various parasitic 
skin diseases such as tinea and scabies. Too irritating for acute inflam- 
mations of the skin, it certainly exerts a powerful effect on recent 
cell infiltrations, and is extraordinarily successful in chronic and 
subacute eczema, where there is much thickening from exudation, 
in seborrhea, and even in psoriasis and pityriasis. It is preferably 
used in solution; from ten to thirty grains in one drachm of alcohol, 
one drachm of glycerin, and eight drachms of water, well sopped on 
the part and allowed to dry. According to Andeer, resorcinol, in 
powder or in saturated ethereal solution, is a feeble caustic, useful 
in the treatment of chancres, of papilloma, and even of epithelioma 
and diphtheria. Dose, two to five grains (0.13-0.3 dm.). 

Oxalic Acid. — The chief interest of this substance to the medical 
profession is as a poison. Oxalic acid is a paralyzant to the respira- 
tory, vaso-motor and spinal motor centres (Rabuteau and Kobert 
and Kiissner). It is also a cardiac poison, arresting the heart in sys- 
tole. The acid is eliminated by the kidneys. As a poison, oxalic 
acid figures in two forms: that of simple oxalic acid, and that of the 
acid potassium oxalate, or salt of sorrel, or essential salt of lemons, as 
it is variously termed in common parlance. The symptoms produced 
are a hot acrid taste experienced during the swallowing, a burning 
in the gullet, soon extending to the stomach, intense abdominal pain, 
vomiting of highly acid, greenish, blackish-brown or bloody mucus 
(rarely of arterial blood), collapse, livid surface, cold skin, entire 
prostration of strength, small, irregular pulse, stupor, unconscious- 
ness, sometimes convulsions, and finally death. In some cases the 
gastric symptoms are very prominent; in others they are nearly 
wanting, and the chief manifestations are collapse and such nervous 
symptoms as almost complete general paralysis, numbness, and 
finally stupor; indeed, the patient may suddenly fall unconscious 
immediately after the ingestion of the poison. Nephritis and oxaluria 
are probably constant symptoms and glycosuria has been noted by 
Kobert and Kiissner and by Sarganeck.* In pregnant women 
abortion or at least death of the fcetus usually occurs. 

Taylor states that the smallest quantity which is known to have 
caused death is one drachm. An ounce usually proves fatal, but has 
been recovered from. After death the coats of the stomach are found 
softened and swollen, and sometimes perforated. Rabuteau affirms 
that the blood is everywhere scarlet; but this is certainly not always 
the case (Taylor). According to Kobert and Kiissner, a pathog- 
nomonic post-mortem lesion is the incrustation of the urinary tubules 

* Kobert has marie the very important observation, that the extract of Syzygium jambolanum 
will control the glycosuria produced by oxalic acid. 



686 EXTRANEOUS REMEDIES 

with crystals of oxalates. In poisoning by oxalic acid, the immediate 
administration of an antidote is of the utmost importance. 

As the potassium and sodium oxalates are poisonous, neither 
potash nor soda is available; but, fortunately, lime or chalk is a 
perfect antidote to oxalic acid, forming the excessively insoluble 
calcium oxalate. As time is a matter of so much importance, tooth- 
powder, chalk, "whitewash" off a wall, or a fence, or whatever form 
of lime be at hand should be rubbed up with water and administered 
freely. The after-treatment is that of toxic gastro-enteritis. 

As an emmenagogue, oxalic acid has been used in all forms of 
amenorrhea with asserted great success. It is said also to be an active 
abortifacient, but as such is certainly extremely dangerous. The 
dose usually given is half a grain three or four times a day, but F. W. 
Talley has reported serious poisoning as produced by this amount. 

Oxalic acid is a powerful germicide. According to 0. Loew, the 
one-per-cent. solution of the neutral potassium oxalate is very active 
in the destruction of infusoria, while Howard A. Kelly asserts that 
potassium permanganate and oxalic acid afford the only known 
practical means of disinfecting the surgeon's hands. * 

FORMALDEHYDE. 

Formaldehyde, formyl or formol, is a gaseous body which is 
obtained by the oxidation of methylic alcohol at moderately high 
temperature, as by passing the vapors over red-hot metal or carbon. 
It readily dissolves in water and alcohol, forming a colorless fluid, 
having a peculiar, pungent odor and an unpleasant taste. 

Solution of Formaldehyde (Liquor Formaldehydi) contains not 
less than thirty-seven per cent., by weight, of absolute formaldehyde, 
which is the strongest permanent aqueous solution that can be made. 

Physiological Action. — Local Action. — Absorption and Elimina- 
tion. — Formaldehyde is an intensely active local irritant, producing 
even when in very minute amount in the air violent irritation of the 
respiratory mucous membrane, or, it may be, fatal pulmonary inflam- 
mation. It is also a very active coagulant of albumin and gelatin 
when in at all concentrated form; and when added to blood it causes 
an immediate coagulation, with a serum so strongly colored red as 
to suggest destruction of the red blood-corpuscles, though it may be 
that the color is due simply to the squeezing out of the corpuscles 
from the clot. According to Mosso and Paoletti, however, when 
added in a very dilute form to an albuminous solution, formaldehyde 
not only does not coagulate the albumin, but so acts as to prevent 
the coagulation of albumin by heat. It is therefore capable of absorp- 
tion, and the statements made that the urine passed by animals to 

* The method practised by Kelly is as follows: 1. Scrub the hands for ten minutes in hot 
water frequently changed. Immerse in a saturated solution of potassium permanganate, until 
every part of the hands and lower forearms is stained a deep mahogany red or almost black color, 
transfer to a saturated solution of oxalic acid until completely decolorized and of a healthy pink 
color. Wash off the oxalic acid in warm sterilized water. 



DISINFECTANTS 687 

which it is given even in moderate quantities is incapable of putre- 
faction indicate that it is not only absorbed, but also eliminated 
unchanged from the kidneys. 

The discovery by Trillat, in 1888, that formaldehyde is a powerful 
germicide, has been abundantly confirmed, but its activity has been 
greatly overestimated. The more recent investigations indicate that 
it is not much stronger than is phenol. 

According to Burgess, a two-per-cent. solution of formaldehyde kills the bacillus 
ooli communis in five minutes. In the experiments of Slater and Rideal it required 
fifty minutes for a one-per-cent. solution to kill the staphylococcus pyogenes aureus 
or bacillus typhosus, and thirty minutes to destroy the bacillus coli communis. 
Clothing soaked twenty-four hours in a 1:1000 solution was not always sterile, but 
after being exposed to a one-per-cent. solution was always sterilized. 

As regards the effect of the formaldehyde vapor in disinfecting a room, Slater 
and Rideal found that after the evaporation of one and one-half ounces of a forty- 
per-cent. formaldehyde solution in a room of fifteen hundred cubic feet there was 
a marked diminution of the number of organisms found in the dust, although they 
were not all destroyed. According to Trillat, one pound of a forty-per-cent. for- 
maldehyde solution is sufficient to disinfect an ordinary-sized room. Kenwood has 
determined that when formaldehyde vapor is present in the air in the proportion of 
one and one-half to two per cent, there is complete and rapid disinfection of all the 
surfaces. Woodhead found that the vaporization of one pound of forty-per-cent. 
formaldehyde solution, by means of a special form of apparatus, destroyed all 
exposed cultures, including the spores of the anthrax bacillus, but that pieces of 
folded linen were not always completely sterile. In a lamp generating formalde- 
hyde directly from methyl alcohol, according to Kenwood, it requires one and one- 
half litres of alcohol to disinfect a room of two thousand cubic feet. A popular and 
convenient form of formaldehyde generation is through the heating of tablets of 
paraformaldehyde. According to Rideal, one gramme per thousand cubic feet of 
paraform did not kill the bacillus coli communis in four hours. Four grammes per 
thousand cubic feet of air space killed the test-germs which were exposed on silk 
threads, but not cultures soaked into paper slips. Ten grammes of paraform per 
one thousand cubic feet killed various non-sporing micro-organisms, both exposed 
and when wrapped inside of rolls of linen. The spores of the anthrax bacillus and 
bacillus subtilis were usually but not invariably destroyed by twenty grammes per 
thousand cubic feet. 

In an elaborate investigation made in 1903 by Ravenel and Gilliland the value 
of formaldehyde as a germicide was abundantly reaffirmed, and the importance of 
the abundance of moisture in the air with the formaldehyde vapor, and the value of 
high temperature when it can be obtained as assisting in the action of formaldehyde, 
were made very apparent. The theory of Van't Hoff, that formaldehyde acts as a 
bactericide by the formation of an active oxygen, has been disproven by Waldemar 
Koch, and it would appear that it acts directly. 

According to the experiments of Aronson and of Burkhard formaldehyde not 
only is a germicide, but also has the power of destroying the toxins of diphtheria, 
of tetanus, and probably of other diseases. 

General Effects. — The violent irritation produced by formaldehyde 
is so immediate that accidental or purposive poisoning by it is very 
rare. The general action of the drug is evidently feeble, as it produces 
more serious symptoms when given by the mouth than when injected 
hypodermically (Mosso and Paoletti). 

Trillat states that sixty-six centigrammes of formalin per kilogramme given to 
the guinea-pig arc not mortal, although the urine passed by the animal is incapable 



688 EXTRANEOUS REMEDIES 

of putrefaction; while the intravenous injection of thirty-eight centigrammes per 
kilogramme causes in the rabbit no pronounced symptoms. According to Mosso 
and Paoletti, fifty cubic centimetres per kilogramme injected hypodermically pro- 
duce in the dog severe poisoning, with fall of temperature, ending after many days 
in death; the same amount given by the stomach causes in the dog violent con- 
vulsions, general rigidity, salivation, and in a short time death, preceded by stupor 
and unconsciousness. 

In J. Kliiber's case of poisoning the patient, a man, was found unconscious 
and supposed to be suffering from apoplexy. The coma lasted for many hours, 
going off gradually in a stupor. The urine was suppressed for nineteen hours, and 
formic acid, but neither sugar nor albumin, was found in it. L. Zorn reports a 
case with burning in the mouth and stomach, nausea, mild cyanosis, albuminuria, 
and difficulty of breathing. 

According to Mosso and Paoletti, small doses cause rise in the 
blood-pressure, probably as the result of peripheral contractions of 
the arteries; while toxic doses depress the circulation and so act 
upon the blood that on exposure it coagulates instantly, with the 
separation of a dark red serum. 

Therapeutics. — On account of the safety connected with its 
use, its activity, its permanence of constitution, and its lack of 
destructive action on vegetable and animal substances, formaldehyde 
is probably the most reliable and the most generally useful of all the 
germicides when it is not necessary to bring the agent in contact 
with the human body. It does not affect either the color or struc- 
ture of clothing or other materials in common use. Its vapor, being 
of low specific gravity, mixes readily with the air, and penetrates 
loose fabrics much more deeply than does any other known germicide. 

Using an apparatus invented by himself for the production of formaldehyde 
directly from methyl alcohol, Trillat foimd that it was possible completely to dis- 
infect rooms and the furniture contained therein in six hours, by the consumption 
of from four to six litres of the alcohol for each three hundred cubic metres of the 
room. In 1895 Van Ermengen and E. Sugg sterilized in a room books and other 
small objects containing the germs of diphtheria, tuberculosis, scarlet fever, small- 
pox, etc., by means of formaldehyde evaporated from its aqueous solution in such 
quantity that there was about the value of five cubic centimetres of formaldehyde 
in one litre of air, and in 1896 it was demonstrated by E. G. Horton that infected 
books shut up in a closed space could be disinfected in fifteen minutes by the vapor 
of commercial formalin, — one cubic centimetre of the formalin to three hundred 
cubic centimetres or less of air, — and that the books were not in any way injured by 
the process. More recently there has been abundant confirmation as to the activity 
of formaldehyde, which, when properly used in a room with moistened air, fails only 
when the objects are so dense or in such mass that they cannot be penetrated. 

It has been shown in an elaborate series of experiments by Herzog 
that the addition of formaldehyde vapor enormously increases the 
disinfective power of steam, but that this increase of power does not 
influence the disinfection of massive objects; the outer layers of the 
object apparently absorbing all the formaldehyde out of the vapor, 
so that inside of a bundle of blankets the effect would be simpty that 
of pure moist heat. Vapor at 70° C, containing one per cent, of for- 
maldehyde, was found to kill spores in four minutes which were 
able to resist the action of simple watery vapor at 98.5° C. for nine 
minutes without injury. 



DISINFECTANTS 689 

In disinfect inn an apartment, windows, doors, chimneys, vent: 
lators, and similar openings should be tightly closed, while the air 
should be made to contain at least one per cent, of formaldehyde gas, 
and at the end of twenty-four hours, when the apartment may be 
opened, should still be strongly impregnated. The gas may be 
obtained by the pulverization of formalin or other solution of formal- 
dehyde, but not by the simple evaporation of the solution, since the 
formaldehyde, upon the application of heat, becomes largely poly- 
merized into a solid, paraform * which gives off formaldehyde slowly 
and in small quantities. It is stated that the addition of glycerin to 
the solution of formaldehyde prevents the polymerization by heat 
of the formaldehyde, so that the so-called glycoformalin (formal- 
dehyde thirty parts, water sixty parts, glycerin ten parts) is 
preferable to the aqueous solution, although its use has the dis- 
tinct disadvantage of leaving many articles in the room sticky from 
a coating of glycerin. 

The intense activity of formaldehyde as an irritant greatly interferes with its 
use upon the human body. The application to an ulcerated surface of even its one- 
per-cent. solution causes intense pain lasting for a considerable length of time. 
Nevertheless, formaldehyde is employed to a considerable extent by practical 
surgeons in cases of tubercular abscesses, infected wounds, and infectious inflammations 
of the mucous membranes. In many instances it is better to apply a strong solution 
once or twice than to use a weaker solution more frequently, although a one- to five- 
per-cent. solution is spoken of by various surgeons as singularly effective. By the 
previous application of cocaine the pain normally produced by the formaldehyde 
may be prevented, and there is no danger of systemic-poisoning by even the strongest 
solution. The two-per-cent. solution of formaldehyde is very effective for the dis- 
infecting of the hands of the surgeon, but has been found too irritating to be prac- 
tical. A one- to two-per-cent. solution is sometimes employed for the rendering of 
instruments aseptic, but its use is usually less convenient than that of a simple 
chamber in which by means of heated paraform the instruments may be disinfected. 
It is stated that by the employment of this apparatus instruments contained in a 
chamber one cubic foot may be absolutely disinfected in fifteen minutes by the 
evaporation of five grains of paraform at a cost of one cent. 

The use of formaldehyde for the preservation of milk and other 
articles of food does not seem to us justifiable; although when 
employed in the proportion of 1:5000 to 1:10,000 it does not affect 
the taste. It has been shown by A. G. R. Foulerton f to make milk 
less digestible, and also by F. W. Tunnicliffe and O. Rosenheim 
to distinctly affect assimilation in weak children, and probably to 
increase the destruction of nitrogen. In all cases observed by these 
investigators the amount of lecithin in the feces was diminished by 
the formaldehyde. 

Formaldehyde has been used to some extent in human medicine 
as a local germicide in various infective diseases, and as a caustic in 
inoperable cancer, also by inhalation in pulmonary tuberculosis and 
chronic bronchitis, but its value is questionable. 

* Paraform, or polymerized formaldehyde, is a colorless, crystalline powder insoluble in water, 
of very stable constitution, which when heated slowly gives off formaldehyde gas. 
t See also Bliss and Novy, J. Ex. M., iv, 

M 



690 EXTRANEOUS REMEDIES 

Formalin has been used as an intravascular germicide, but its 
value has not yet been determined. It does not seem probable, a 
priori, that the treatment should be beneficial because a quantity 
sufficient to exercise any distinct antiseptic action cannot be injected 
without jeopardizing life. In the investigations of Fortescue-Brick- 
dale, intravascular injections of formaldehyde were of no service in 
rabbits infected with pneumococcus or with the anthrax germ; and 
similar results were reached by W. H. Park with rabbits infected with 
pneumococci and streptococci. C. C. Barrows, however, in one case 
of violent human septicemia, believed that life was saved by the intra- 
venous injection of formaldehyde; and a similar case is reported by 
W. F. Honan. In these cases 500-700 C.c. of a solution of formalin 
(1:5000 sterile physiological salt solution) were thrown slowly into 
the veins. 

Volatile Oils. — The general properties of volatile oils have been 
already mentioned in the section on Aromatics (see page 478). 
Cadeac and Meunier * give the following table as representing the 
time which it requires the pure volatile oils to destroy the typhoid 
bacillus: 

At the End of I At the End of 

Cinnamon of Ceylon 12 minutes Geranium of France 50 minutes 

Cloves 25 minutes ! Zedoary 2 hours 

Eugenol 30 minutes 

Thyme 35 minutes 



Absinthe 4 hours 

Sandalwood 12 hours 



BENZOIN. 

The concrete juice of Styrax Benzoin, a large tree, native of Siam. 
The drug is said to be obtained by incising the tree and allowing the 
juice to harden as it exudes. The finest specimens of benzoin consist 
of tears agglutinated together; the poorest, of brown or blackish 
masses without tears. The fracture is resinous, the surface of the 
tears smooth and whitish, the odor fragrant, the taste at first very 
slight, afterwards somewhat acrid. The chief constituents of benzoin 
are resin and benzoic acid; cinnamic acid is also frequently present. 

Benzoic Acid is obtained by sublimation of gum benzoin. As thus 
prepared, it is in white feather}^ crystals, of a silky lustre, a warm, 
peculiar taste, and a fragrant vanilla-like odor, due to the presence of 
a volatile oil, the pure acid being inodorous. It is almost insoluble 
in water but its ammonium and sodium salts are freely soluble. 

Benzoic acid is widely distributed through the vegetable kingdom, constituting 
the peculiar principle of all true balsams, and is occasionally present in the urine 
of grass-eating animals. It is a normal constitutent of castor, and has been 
detected by Seligsohn in the suprarenal capsules of an ox. It is used considerably 
in the arts, and for this purpose is prepared from the allied hippuric acid of horse 
urine, and also, it is said, from naphthalin: these forms of the acid should never 
be used medicinally. 

* Quoted by Sternberg (Text Book of Bacteriology, N. Y., 1896, p. 199). 



DISINFECTANTS 691 

Official Preparations : 

Tinotura Benaoini (20 per cent.) J to 1 fluidraehm (2-4 C.c). 

Tinctura Benzoini Composite (10 per cent.) . . l to 2 fluidrachms (l -8 C.c). 

Aciduin Menzoieuin 10 to 30 grains (0.6-2 dm.). 

Ammonii Benzoas 10 to 150 grains (0.6 _' Gm.). 

Sodii Benzoas 10 to 30 grains (0.6-2 Gin.). 

Physiological Action. — Local Action. — Benzoic acid, unless in 
large quantities and pure, is scarcely irritant to mucous membranes, 
on which, however, it exerts a distinctly alterative influence. As a 
germicide it is quite active, but less powerful than salicylic acid. 

Absorption and Elimination. — Benzoic acid is absorbed rapidly, 
and, as was first discovered in dogs by Wohler, and afterwards in 
man by Ure, it is eliminated chiefly from the kidneys, united with 
nitrogenous atoms, as hippuric acid.* 

It has not yet been determined where in the body the hippuric acid is formed, 
nor yet has the source of the nitrogen been made out. Lewandowsky in five exper- 
iments found that although an enormous amount of hippuric acid was excreted 
there was no lessening in the elimination of uric acid, and hence concludes that 
there is no relation between the formation of the two acids. It has been suggested 
by Kuhne and Hallwachs that the conversion occurs in the liver; but the researches 
of Meissner and Shepard appear to show that it really takes place in the kidneys. 

The conversion does not happen in the intestines or in the blood, since after 
the exhibition of large doses of benzoic acid it alone can be detected in the blood; 
and after the administration to rabbits of large amounts of hippuric acid by the 
mouth, only traces of the latter, with large quantities of benzoic acid, can be found 
in the blood, although the hippuric acid appears in the urine;f further, moderate 
amounts of hippuric acid injected into the blood cause severe symptoms of poison- 
ing, which is not true of benzoic acid. When benzoic acid is injected freely into 
the blood, a portion escapes through the kidneys unchanged. J G. Bunge and O. 
Schmiedeberg have also found that in the dogs with renal arteries tied no conversion 
of benzoic into hippuric acid occurs, but that tying of the ureters does not interfere 
with the change and have succeeded in converting benzoic into hippuric acid by 
passing blood containing benzoic acid, with or without glycocoll, slowly through 
the kidneys, removed from the body directly after death. From some of their 
experiments it would seem that the blood-corpuscles play an important role in the 
process, as when serum freed from blood-corpuscles was used, at most only a trace 
of hippuric acid was formed. According to Meissner and Shepard, sometimes the 
benzoic is converted into succinic instead of hippuric acid in man, and in chickens 
it is habitually changed into new products, one of which is nitrogenous. 

General Effects. — The influence of benzoic acid upon the general 
system is very slight. The largest therapeutic doses never produce 
any symptoms, unless it be those of slight gastric irritation; a half- 
ounce of the acid taken by Schreiber in two days caused only an 
increased rapidity of the pulse-beat and moderate disturbance of 
digestion. 

* Gusseron found hippuric acid in the urine of a new-born child when benzoic acid had lieon 
given to the mother just before the birth (Hoffmann und Schwalbe's Jahresb., 1879, 283). The 
experiments of Von Schrader and of Mosso (Arch. Exper. Path. u. Pharm., 1889, xxvi.) seem to show 
that the whole of the ingested benzoic acid escapes with the urine. 

t For a general summary, see paper by Van de Velde and Stokvis (Arch. f. Exper. Path. u. 
Pharm., xvii. 189). V. Poulet (Bull. tioc. de Med. Prat., 1888) uses the hippurate of lime and lithia, 
affirming that they are much superior to the benzoates in ammoniacal cystitis. 

t According to the experiments of Th. Weyl and B. von Anrep, if benzoic acid be given to 
man or animals in a febrile state a much larger proportion of it than usual is eliminated unchanged 
(Hoffmann und Schwalbe's Jahresb., 1881, 447). 



692 EXTRANEOUS REMEDIES 

W. Grube states that in massive doses (1 to 5766 of the animal's weight) it 
produces intoxication, with disturbance of circulation and respiration, and paralysis 
of the hind feet, and that the antipyretic influence of benzoic acid is greater than 
that of salicylic acid. 

Nutrition. — Some authorities have believed that benzoic acid 
distinctly affects nutrition, but the testimony as to the action of the 
acid upon the elimination of urea and uric acid is so contradictory 
as to indicate that it has no constant powerful influence upon 
protoplasmic activities or upon nitrogenous elimination. 

Ure, Leroy d'Etoilles, and Debouy (quoted by Stille) affirm that the uric acid 
is very much diminished or altogether absent, while Garrod and Keller assert that 
its quantity remains normal. Again, Garrod affirms that the urea is very much 
diminished in quantity, Keller and Meissner and Shepard declare that it is not 
affected, and in the elaborate experiments of Carl Virchow, sodium benzoate caused 
a decided increase of the nitrogenous elimination from the kidneys. 

It is commonly asserted by clinicians that the acidity of the urine 
is increased by the administration of benzoic acid, and it is probable 
that the disappearance of uric acid crystals from the urine under the 
influence of the drug is due to the conversion of insoluble uric into 
soluble hippuric acid. W. W. Ashhurst asserts as the results of experi- 
ments made with sodium benzoate, that this salt does not increase 
the acidity of the urine, and that the mistake of clinicians has arisen 
from the fact that in cystitis the urine has its acidity increased by 
the drug because the ammoniacal fermentation is checked by the 
benzoic acid. 

Antiseptic Influence. — In April, 1872, Dougall announced that 
benzoic acid is an active antiseptic. Since that time, numerous 
experiments have been made by E. Salkowski, Grube, Bucholz, and 
Fleck, with the unanimous result of ascribing to benzoic aci' 1 a first 
rank in destroying bacteria and preventing putrefaction. In most 
of these investigations benzoic acid was shown to be much more 
active than salicylic acid. Bucholz found that 0.02 per cent, of 
benzoic acid has a very perceptible effect upon the development 
of bacteria, and 0.1 per cent, inhibits their growth entirely; also 
that the sodium benzoate is no less powerful than the pure acid. 
Kumagawa determined that benzoic acid acts powerfully as an 
intestinal antiseptic, notably reducing both the indican in the 
urine and the number of the bacteria in the intestines. 

Therapeutics. — Benzoic acid is a valuable remedy in subacute 
nasal and respiratory catarrhs, also in chronic bronchitis. As an anti- 
zymotic it is considerably used by the Germans in diphtheria, ery- 
sipelas, and allied diseases. Senator, of Berlin, alleges that in daily 
doses of about three drachms it is equal in acute rheumatism to salicylic 
acid. Ure first suggested the employment of benzoic acid in uric 
acid gravel and calculus, because, as he thought, it diminished the 
excretion of uric acid; and Golding Bird subsequently asserted that 
his clinical experience had shown the value of benzoic acid in uric 



DISINFECTANTS 093 

acid diathesis. It certainly i.s often effective in causing uric acid 
crystals to disappear from the urine. In the phosphatic urine of 
vesical catarrh benzoic acid often acts most happily: it checks fer- 
mentation in the urine, aids in the solution of the phosphates, and 
acts upon the mucous membrane of the bladder as an alterative 
antiseptic. In ammoniacal cystitis the drug is of great value. It is 
also said often to act very happily in acute gonorrhoea. 

Benzoic acid has the property of preventing animal fats from 
becoming rancid, and is therefore much used as an addition to oint- 
ments. Moreover, it exerts a peculiar, often very beneficial, stimu- 
lant action upon the skin, and is very useful in such conditions as 
chapped hands, lips, or nipples, and even in fissure of the anus. 

There would seem to be no doubt that benzoic acid may be sub- 
stituted for phenol or salicylic acid in antiseptic surgery. Under the 
name of balsamum traumatkum, a preparation practically the same 
as the compound tincture of benzoin, was formerly much used as a 
vulnerary. The practice has gone out of vogue, but the discoveries 
concerning antisepsis show that it was well founded. 

Cinnamic acid is present in Peru and Tolu Balsam, but for commercial pur- 
poses is prepared synthetically. It is insoluble in cold water, but freely soluble in 
boiling water and alcohol. It has been used in medicine solely in the treatment of 
tuberculosis, especially in the form of sodium, cinnamate (Hetol). 

As originally suggested by A. Landerer, the salt, is to be given intravenously, 
and, according to Tobias, the same vein may be injected from fifty to sixty times in 
succession. Most extraordinary results have been claimed for the method, Lan- 
derer affirming that in the early stages of uncomplicated tuberculosis eighty-five 
per cent, of the cases can be cured. The heated controversy which Landerer's 
paper gave rise to has been well reviewed by W. J. Robinson. It does not appear 
probable that the Landerer treatment will accomplish what is claimed for it, and 
the conclusion of Robinson, that sodium cinnamate is not a direct curative agent in 
tuberculosis, and is of no more value, symptomatically, than is creosote, is probably 
correct. The sodium cinnamate may be given by the mouth in doses of from two 
to three grains. The initial dose of the intravenous treatment should not exceed 
one-fiftieth of a grain; the injection may be made every third day, and the amount 
increased until one-third of a grain has been reached. A ten-per-cent. solution in 
glycerin affords an excellent method of administration. 

VI.— SULPHUR AND BORON COMPOUNDS. 

SULPHUR. 

Sulphur* is a yellow amorphous solid insoluble in water, but 
soluble in alkaline solutions, alcohol, the fixed and volatile oils, 
chloroform, ether, etc. 
Official Preparations: 

Sulphur SubUmatum | ^ an alterative> 10 to 20 grains (0 ^ 2 Gm) 

bulphur ^otum > ^ & laxati x to 2 drachms ( 4 - 8 Gm.). 

Sulphur Praecipitatum J 

Unguent urn Sulphur is (15 

per cent.) External use. 

Sulphuris Iodidum Not used internally. 

♦For an account of the various allotropic forms of sulphur, and its chemical properties, the 
reader is referred to works on chemistry. 



694 EXTRANEOUS REMEDIES 

Physiological Action. — Sulphur, itself, is probably an inert 
substance. Such changes as occur after its introduction into the 
intestinal tract are probably due to the formation of hydrogen sulphide. 

When in sufficient quantity, sulphur acts as a mild laxative, producing soft, 
semi-liquid, feculent stools, accompanied generally by much offensive flatus of 
sulphuretted hydrogen. It is affirmed that in some instances the latter gas has been 
so freely generated and absorbed as to cause systemic poisoning. Its continued 
use has perhaps some effect upon nutrition; the secretions generally are slightly 
increased, and some have affirmed that the temperature is somewhat elevated; but 
the truth of this is certainly very doubtful. The oxides it forms are, however, at 
least locally, active bodies. 

Therapeutics. — As an habitual laxative, sulphur has been used 
with asserted advantage in cases of hemorrhoids and of chronic rheu- 
matism. It has also been employed as an alterative in both rheu- 
matic and skin diseases. It is affirmed by Doit that the natural 
sulphur-waters are of very great value in the treatment of chronic 
syphilis, as they undoubtedly are in chronic gout and rheumatism.. 

The known germicidal properties of the sulphur compounds 
indicate that it should have value as an intestinal germicide, and it 
has been found to be of very great service by the U. S. medical officers 
in the Philippines in the treatment of the chronic amoeboid dysentery 
of that country. It has also been highly commended by Woroschilsky 
in typhoid fever. In either case from ten to fifteen grains may be 
given in capsules every three to four hours. 

Sulphur is chiefly used as a parasiticide in cases of itch and 
other skin infections. 

Sulphurated Lime. — Calx Sulphurata. — Commercial Calcium Sulphide. — A 
mixture containing, according to the requirements of the U. S. Pharmacopoeia, 
at least fifty-five per cent, of calcium sulphide together with unchanged calcium sul- 
phate and carbon in varying proportions. It has been strongly recommended by 
Sydney Ringer, by Duhring and others, for the treatment of successive crops of 
boils, and in scrofulous and other unhealthy sores and glandular enlargements in 
children. Official dose, one grain (0.06 Gm.). 

SULPHUROUS ACID. 

Sulphurous Acid of the U. S. Pharmacopoeia is a six-per-cent. 
(by weight) solution of sulphur dioxide (sulphurous acid gas) in 
water. It is a colorless liquid, with an acrid sulphurous taste, and the 
characteristic odor of burning sulphur. A somewhat elaborate study 
of the action of the sulphites upon vertebrata has been made by 
Pfeiffer, who finds that they are poisonous when in very large doses, 
but that the rapidity with which they are oxidized into the sulphate 
frequently brings about sudden recovery in the deepest condition of 
poisoning. In sufficient amount they are said to paralyze the 
blood-vessels, the heart, and the respiratory apparatus. 

Official Preparations: 

Acidum Sulphurosum Not used internally. 

Sodii Sulphis 15 to 60 grains (1-4 Gm.). 

Sodii Bisulphis 10 to 30 grains (0.6-2 Gm.). 



DISINFECTANTS 695 

Sulphurous acid and its salts arc most efficient in destroying the 
low forms of life which are connected with putrefaction and fermen- 
tation, and for this reason are preservatives of organic matters; they 
arc also among the oldest of disinfectants, having been used as long 
ago as 1771; but recent experimental evidence indicates that they 
have not the great superiority which has been attributed to them. 

According to the experiments of Sternberg, 1 volume of sulphurous acid gas 
in 1(H) volumes of air is sufficient to disinfect dry vaccine matter. As these experi- 
ments are in accord with older observations, they may be considered as correct. 

According to Wcrnitz, the action of pepsin, of ptyalin, of invertin, and of dias- 
tase is prevented by the presence of an aqueous solution of sulphur dioxide; of 
1:1317 to 1:8600 (by weight); while the action of myrosin and of emulsin is neu- 
tralized by 1:21,000. Wernitz further says that strips of woollen or cotton goods 
saturated with putrefactive matter are disinfected by exposure of from four to six 
hours to an atmosphere containing four per cent, of sulphur dioxide. The very 
elaborate experiments of Koch, of Wolffhugcl, and of Sternberg have shown, how- 
ever, that when the infectious material contains spores sulphur dioxide is of very 
little efficiency. 

Sulphurous acid may be produced very cheaply upon a large 
scale by the burning of sulphur, and its vapor when thrown with 
steam into the hold of a vessel mixes with the water of the vessel 
and with the condensing steam, penetrating into all the cracks and 
places where the disease-germs may have found resting-place. It 
does not readily undergo decomposition; its ordinary salts are germi- 
cidal, and it is still relied upon for the disinfection of infected ships. 
On the other hand, in an ordinary room it does not find water in 
which to dissolve; it is liable seriously to impair clothing, bedcloth- 
ing, and other organic material of value; and as formerly made, by 
burning in a simple iron pot, it was ineffective; so that the purifica- 
tion of apartments by burning sulphur in the house has been entirely 
displaced by the use of formaldehyde. 

The sulphites and bisulphites have been largely employed to arrest 
or control fermentation, and are useful in saturated solution in 
various parasitic diseases of the skin. 

BORIC ACID. 

Boric (or Boracic) acid crystallizes in white translucent scales, 
soluble in eighteen parts of cold water, much more soluble in boiling 
water, which on cooling precipitates all but about twenty-three 
grains to the fluidounce. Hot glycerin dissolves and holds upon 
cooling as much as three drachms to the fluidounce. Sodium Borate 
occurs in white, flattened, prismatic crystals, soluble in seventeen 
parts of cold water. A. Dujardin states that borax is incompatible 
with the alkaloids. 

Official Preparations : 

Acidum Boricum 10 to 20 grains (0.6-1.2 Gm.). 

Glyceritum Boroglycerini (31 per cent.) External use. 

Sodii Boras [Borax] 15 to 30 grains (1-2 Gm.). 



696 EXTRANEOUS REMEDIES 

Physiological Action. — Local Action. — Locally, boric acid is, 
when in concentrated form, distinctly irritant; in dilute solution, 
stimulant and antiseptic, and having even a soothing influence upon 
mucous membranes. Its sodium salt even in concentrated form is 
scarcely irritant. The germicidal power of boric acid and its salts 
is too feeble to be relied upon in cases of serious infection. 

In 1874 Dumas and Schnatzles announced that borax is poisonous to the lower 
forms of life. In Bucholz's experiments, 0.75 per cent, of boric acid was found 
sufficient to prevent the development of bacteria. In the experiments of Walb, 
a two-per-cent. solution of borax distinctly checked the putrefaction of solution 
of fibrin; a five-per-cent. solution kept the solution fresh for nineteen days. Fresh 
muscle-fibres from oxen were kept fresh many days by a one-per-cent. solution. 
Sternberg found that boric acid and sodium biborate are inefficient as germ- 
destroyers, but have considerable antiseptic power. The experiments of Sternberg 
have received corroboration from E. Andrews. 

Absorption and Elimination. — Boric acid and its soluble salts are 
freely absorbed and eliminated, escaping to some extent with the 
perspiration, saliva, and feces, but chiefly through the kidneys. In 
the elaborate experiments of Chittenden and Gies, twenty-four to 
thirty-six hours were found to be generally sufficient for the com- 
plete removal of the drug, which showed no tendency to accumulate 
in the body. W. Straub, on the other hand, affirms that twelve 
hours are required for the elimination of half, two to three days for 
the complete throwing off the whole of the single large dose. 

General Effects. — The general physiological action of boric acid 
and its salts is very feeble; doses of one hundred and fifty grains of 
borax a day ordinarily producing no distinct symptoms.* Poisoning 
has, however, resulted from the too free use of the drug; the symp- 
toms have varied somewhat, but in most if not all the cases there 
have been great depression of spirits, fall of bodily temperature, a 
very feeble pulse, — rapid or slow, — and an erythematous or a papulo- 
vesicular eruption accompanied by much swelling of the parts, and 
especially affecting the lower extremities and followed by exfoliation ; 
nausea, violent vomiting, and hiccough have been present in some 
cases; ecchymoses have been noted; the mind usually remains clear 
until late in the poisoning, but death has been preceded by coma, 
with disturbances of the respiration and involuntary discharges.! 

Serious boric-acid poisoning is very rare, and we have no knowledge as to the 
amount required to cause death. £ The cases whose report we have met with are:- 
George T. Welch, two ounces of boric acid in the vagina, — recovery; Mododewkow, 
death from washing out internal cavities with five-per-cent. solution; Hogner, 
death from washing the stomach with two- and a half-per-cent. solution. 

* G. Lemoine reports (Bull. Gen. Therap., May, 1892) a bluish-gray line, like that of lead 
poisoning, as present upon the gums in cases of epilepsy in which borax had been given very freely 
and continuously. 

t A very curious effect is said (Schiff, Rev. Med. de Suisse Rom., 1881, 244) to be produced 
by the local application of boric acid to nerves: the part affected is affirmed to lose its power of 
originating but not of transmitting impulses, so that if the galvanic current be applied to the part 
of the nerve which has been exposed to the drug no muscular contractions result, but if the poles 
be placed above this part the distal muscles respond at once. 

t For mild cases see T. G., Oct., 1901; also McWalter, L. L., Aug., 10, 1907. 



DISINFECTANTS 697 

In the experiments made by H. C. Wood and E. T. Stewart, 
enormous doses of boric acid salts were found to cause in the frog 
paralysis of voluntary motion and reflex activity, due to I lie depres- 
sion of motor spinal-centres, the nerves and muscles not being affected. 
The saturated solution of sodium quadriborate, brought into direct 
contact with the heart, was feebly depressant, and, injected in enor- 
mous amount into the jugular vein of the mammal, it lowered 
arterial pressure. 

The use of boric acid as a food preservative is a subject of great 
importance, involving enormous commercial interests. In this con- 
nection, however, it cannot be treated in full detail, but we give the 
following outline of the present evidence: 

Boric acid is undoubtedly in sufficient dose capable of killing the lower animals, 
such as fish and frogs, but Liebreich has found that acetic acid is at least twenty 
times as poisonous to fish; and Th. Maass, that common sail, is twice as toxic to 
the frog. Given in sufficient, amount to mammals it is apt to cause gastro-intestinal 
irritation, but E. de Cyon found that borax added to meat may be given to the dog 
up to one hundred and eighty grains a day without disturbance of the general nutri- 
tion. The question involved in the present discussion is, however, not so much 
the effect of the single large dose of boric acid as the influence of the continuous 
use of the drug by man in small quantity. In the experiments of Chittenden and 
Giess 1.3 per cent, of boric acid added to the food of dogs caused no albuminuria, no 
disturbance of the proteid metabolism, and only slight vomiting — the animals 
gaining weight rather than losing under continuance of the diet; one hundred and 
fifty grains of borax per day failed to produce in the dog abnormal urine. More- 
over, Liebreich found that in rabbits killed by borax the kidney structure was intact. 
On the other hand, Jacob Plaut affirmed that boric acid will produce acute paren- 
chymatous nephritis, and Ch. Fere has seen albuminuria, uremia, and death in cases 
of human epilepsy in which borax had been given continuously for a length of time. 
Harrington maintains that the failure to produce toxic effects with boron deriva- 
tives is due to too short periods of observation. He experimented on cats to which 
were administered, over a period of one hundred and thirty-three days, from 0.5-0.8 
gramme of borax. At the end of tin's period every animal, except one which had 
received 0.54 gramme daily, showed pathological changes in the kidney. In the 
studies of Polli eight persons took for forty-five days thirty grains daily of boric 
acid, and then for twenty-three days sixty grains daily without any abnormal 
symptoms being produced. In the investigation made for the United States Depart- 
ment of Agriculture by H. W. Wiley twelve young men were placed under observa- 
tion for repeated periods of thirty to seventy days. Each period was divided into 
three stages: the fore-period, in which the patient was kept on a selected diet in a 
condition of nitrogenous equilibrium, the borax-period in which the same diet was 
continued with the administration of definite quantities of borax or boric acid, and 
the after-period following the withdrawal of the preservatives. There was found 
a diminution in the quantity of nitrogen eliminated by the urine, which continued 
in the after-period, and a distinct augmentation in the amount of phosphoric 
acid in the urine, with loss of bodily weight brought about by borax. The total 
M>lids of the feces were increased and the total solids of the urine diminished during 
the borax periods, and this relation lasted also into the after-periods, 'taken in 
conjunction with the loss of bodily weight, which was an almost constant symptom, 
these results show that the borax had the effect of lessening the assimilation of 
food, very probably through the disturbance of the digestive processes, since when 
more than four or five grammes (one drachm) of borax were taken daily there were 
distinct symptoms of gastric disturbance. Wiley concludes that while the normal 
man can receive quantities of boric acid or borax, amounting to one-half gramme 
daily, for a limited period of time without loss of health, the long continued use 



698 EXTRANEOUS REMEDIES 

of the salts of boric acid creates disturbances of the appetite and digestion. The 
results of Wiley, so far as nitrogen elimination is concerned, are in disagreement 
with those of Gruber, who found that after large doses (5-10 grammes daily) there 
is an increased elimination of nitrogen, phosphoric acid, and sulphuric acid. This 
has been confirmed by Chittenden and Gies. They state that if the doses of boric 
acid did not decidedly exceed fifty grains a day, no influence was exerted upon 
proteid metabolism or the general bodily nutrition, or the kidneys. 

The above summary of the present knowledge shows that the 
evidence in regard to the propriety of using boric acid as a food 
preservative is, as in most questions involving enormous pecuniary 
interests, more or less contradictory, but apparently demonstrates 
that foods preserved by boric acid are much inferior to fresh foods. 
How far, if at all, they are inferior to foods preserved by sodium 
chloride, and especially by potassium nitrate, is uncertain. It seems 
to us doubtful whether boric acid is more deleterious than is salt- 
petre. The fact is that all salt foods are of difficult digestion, and 
that both boric acid and saltpetre are irritant to the kidneys.* 

Therapeutics. — As originally suggested by Rosenthal, boric 
acid has been found to be an efficient remedy in cystitis w'th ammoni- 
acal urine, rendering the urine acid probably by checking the fermen- 
tation. In our own practice great relief has been obtained in the 
cystitis of spinal diseases by washing out the bladder with a few ounces 
of a saturated solution of boric acid after the use of the catheter. 
As a disinfectant and soothing wash its solution is much used in 
conjunctivitis and rhinitis — from five grains to the ounce up to satu- 
ration. Boric acid is also employed as an antiseptic dressing to fresh 
wounds, abscesses, old burns, etc. (See M. Greene.) 

The saturated solution of boric acid has been especially recom- 
mended in phlegmonous erysipelas. Both boric acid and borax are of 
excellent service in aphthous ulceration, diphtheria, and other inflam- 
mations of the mouth, in which crystals of the salt may be allowed 
slowly to dissolve in the mouth. C. F. Folsom has strongly recom- 
mended borax in the dose of fifteen grains three times a day in epilepsy. 
We have tried the remedy carefully in a large number of cases, increas- 
ing the dose until pronounced gastro-intestinal irritation was caused, 
without affecting perceptibly the return or the severity of the 
paroxysms. 

PRACTICAL DISINFECTION. 

It is not proposed to discuss here the many larger questions in 
regard to disinfection, such as the proper care of sewerage, which 
belongs to the province of the sanitary engineer rather than to the 
daily routine of the medical practitioner. It may be well, however, to 
point out that while foul water-closets in cities have long been the 
subject of much attention and discussion, in country districts privies 

* The most important recent publications opposed to the use of boric acid are Borsaure als 
Konservierungsmittel (E. Rost, Berlin, 1903); Wiley, United States Department of Agriculture, 
Bureau of Chemistry, Bulletin No. 84. In favor of it: Boron Food Preservatives, Perkins, Bacon 
& Co., Fleet Street, London; Borax and Boracic Acid (Oscar Liebreich, Berlin, 1899); Wirkung 
der Borsaure und des Borax (Oscar Liebreich, Berlin, 1903). 



DISINFECTANTS 609 

are usually left to their own noisome devices j a condition of total 
depravity which can be readily prevented by simply standing in the 
outhouse a barrel containing one part of lime mixed with three or 
four parts of dry earth; a small shovelful to be thrown into the 
receptacle immediately after use; and by the periodical withdrawal 
of the comparatively inoffensive mass resulting. 

The problems of the practical physician, so far as disinfection is 
concerned, are three in number, as follows: 

First. — The preparation of the room for the reception of the person 
suffering from contagious disease. All closets should be emptied, all 
articles of ornament and unnecessary furniture should be removed, 
and such as is allowed to remain should be free from upholstery, and 
drawers or other receptacles be kept as empty as may be. Carpets 
should be reduced to a single small rug or removed altogether, the 
nurse finding protection for her feet in cold weather by heavily lined, 
soft, high slippers. The ceiling, walls, surbases, floor, and closets, 
should be thoroughly cleaned with abundant soap, washing-soda, and 
hot water, special care being taken with all crevices or joints. 

Second. — Disinfection during occupancy of the room by the patient. 
It is now generally recognized that to attempt the destruction in the 
air of the widely spread germs, such, for example, as exist in a small- 
pox epidemic, is childish, but it is not so universally recognized that 
the effort to destroy organic germs in the air of the room during occu- 
pancy is equally futile. No person can live in an air which contains 
any known germicide in sufficient amount to kill disease germs; and 
the putting of saucers or other receptacles of chlorinated lime about 
a sick room is a medieval barbarity which should never be permitted, 
because it tends to the production of a false sense of security. The 
air of the sick-room must be kept pure by the checking of the dis- 
charge into it of the disease germs, but especially and chiefly by free 
ventilation, not from one room into another, but directly in some way 
into the open air, so that the disease germs may be widely distributed 
and the patient supplied with an abundance of proper breathing 
material. The source of the poisonous germs is the body of the 
patient, and it is a matter of the most vital importance to destroy these 
germs as largely as possible at the point of discharge. In many 
contagious diseases the pathogenetic organisms are thrown off in 
large quantities with the urinary and fecal discharges; often they 
escape through the skin and through the sputum or other infected 
discharges from the body. All such excretions should be poisoned 
as soon as they leave the body; the disinfectant should be placed 
in the receptacle before, not after, it is used. Moreover, the discharges 
should be allowed to stand mixed with the concentrated germicide until 
sufficient time has elapsed for it to kill the organisms. Chamber-pots 
and other receptacles should not be immediately emptied after use. 
To allow any excretion, sputum, or other infected discharge to exist 
for a moment undisturbed is most culpable neglect. Spit-cups, 
urinals, etc., shoidd have the disinfectant in them while waiting for use. 



700 EXTRANEOUS REMEDIES 

As the skin is often the channel of elimination of the disease poison, 
frequent washing of the patient is essential, and care must be taken 
that the water which has been used should not be emptied before it 
has been disinfected.. 

Of all the germicides, by reason of its cheapness and efficiency, 
chlorinated lime is usually preferable for the disinfection of germs in 
discharges. Phenol or formaldehyde may be used. Corrosive subli- 
mate, on account of the ease of its decomposition and of the danger 
of having its solution about the sick room, is scarcely applicable to 
the present purpose. As the cost of chlorinated lime is practically 
nothing it should be used very freely. 

The clothing of the patient should be cotton, and with the sheets 
often changed. In the changing it suffices to place a clean sheet upon 
the floor and throw into it the discarded clothing and bedding, then 
tie the whole into a hard ball and drop it into boiling water without 
opening, and allow it to remain for over half an hour until all organ- 
isms have been destroyed. This method has, however, the objection 
of fixing permanently in the muslin all stains from blood, feces, and 
organic discharges. It is better, therefore, and in a hospital-ward it 
is essential, to throw the personal and bedclothing piece by piece when 
taken off directly into a covered vessel containing a disinfecting 
solution. According to the experiments of A. C. Abbott, corrosive 
sublimate is actively mordant, and should not be used. Chlorinated 
lime, 0.5-per-cent. solution, in cold water, is effective, does not fix 
stains, and though theoretically it should attack the structure of 
various fabrics, practically has no perceptible influence unless after 
repeated immersion. Probably the best disinfectant -solution for 
this use consists of formaldehyde, three parts; common soft soap, 
three parts; cold water, one hundred parts. After two hours' soak- 
ing in such a mixture the clothing must be taken out and well 
washed in water at a temperature not exceeding 100° F. until all 
stains have been removed. 

Absolute cleanliness in regard to the room itself must be strictly 
enforced during the whole period of sickness, and in many cases it 
is advisable to mop the floor, surbases, windows, etc., with water 
containing ten per cent, of formaldehyde. 

Third. — Disinfection of apartments that have been used. The process 
of purifying an infected room naturally divides itself into two parts, 
— first, the killing of the germs; second, the cleaning of the room; 
and these two acts should always follow in the order here given so 
as to lessen as much as possible the danger to the operator and to 
the surrounding habitations which would be caused by the dispersion 
of the active germs. When the room has been thoroughly prepared 
and properly taken care of during its occupancy its purification is 
very simple. First, all clothing and bedding must be disinfected, 
and the most efficient and useful agent in so doing is heat. In cities, 
in quarantine stations, and other places where proper apparatus is 
forthcoming, all articles of the character spoken of should be exposed 



DISINFECTANTS 701 

to the prolonged effect of hot steam in closed chambers. When this 
is not possible, whatever can be boiled without injury should be 
boiled for at least forty minutes. Such articles as cannot be boiled 
may be immersed in a 1:1000 solution of corrosive sublimate overnight, 
or preferably in a twq-per-cent. formaldehyde solution, and then 
thoroughly washed. To those articles of clothing or bedding to which 
none of these processes are available without serious injury, fire should 
be applied if the infection has been at all severe. All articles of furni- 
ture should be washed with a solution of corrosive sublimate, 1:500, 
care being taken to see that the solution is well applied to cracks, 
joints, etc. Twenty-four hours later the furniture may be sponged 
off with an ordinary solution of soap and water. 

In the further purification of the room, it must be remembered 
that it is not chiefly the air which is to be purified but the various 
solid surfaces and bodies on which germs have found lodgement. 
The best of the germicides for this purpose is undoubtedly formalde- 
hyde. It is used in practice in various ways. It is demonstrated 
that the moist gas acts very much better than does the dry, and in 
our opinion the best method of applying formaldehyde is by means of 
a spray or atomizing apparatus, which should throw a finely broken 
spray all over the surbases, walls, floors, etc., so as to bring the for- 
maldehyde in direct contact with the infected surfaces in excessive 
amount. The ordinary spray pump used by fruit-growers suffices 
for an impromptu disinfection, but is better replaced by a special 
atomizer when much work is to be done. The rule of the Philadel- 
phia Health Bureau in regard to the strength and amount of the 
solution to be used seems to us correct. A solution of equal parts of 
water and of the official watery solution of formaldehyde is sprayed 
upon all the surfaces of the room in the proportion of three pints of 
the solution to one thousand cubic feet of air space in the room. 

In lecture-rooms, with abundant benches, and in some other peculiar apart- 
ments, it is possible that this amount of solution would not suffice to cover all sur- 
faces. ' Under these circumstances sufficient of the disinfecting fluid should be used 
to wet every surface in the room. We are informed by Dr. A. C. Abbott, chief of 
the Philadelphia Health Bureau, that they secure by means of the solution, sprayed 
in the manner above related, one hundred per cent, of disinfection, that is to say 
all test objects placed in a room have their germs destroyed by it. It is essential 
that the work be done quickly, and in very large rooms several operators should 
work at the same time; since the liberation and diffusion of the formaldehyde gas 
will very soon drive the operators from the chamber. 

By means of the formaldehyde lamp, or various vaporizers, it is 
possible to disinfect the apartment without the direct use of atomiza- 
tion. If the atomizer be used, one part of a saturated solution of 
formaldehyde may be added to four parts of water, so as to make a 
twenty-per-cent. solution. After the treated room has been shut 
twenty-four hours it may be opened, freely ventilated, and thoroughly 
cleaned with abundant use of fresh water, soap, washing soda, 
scrubbing-brush, and physical exercise. 



702 EXTRANEOUS REMEDIES 

When it is necessary to disinfect a room which has not been prop- 
erly prepared or taken care of during a past illness, the method of 
procedure is in general similar to that just described, but different 
in some minor details. All small articles which can be without injury 
purified by heat, either in the steam-chest or by boiling, should be 
so treated. All articles which cannot be so acted upon without 
injury should be, with the furniture, well washed with the corrosive 
sublimate solution; or if the character of the articles forbids this, 
may be disinfected with formaldehyde. For this purpose the articles 
must be taken out of the drawers and placed in position where they 
will be fully exposed in all their surfaces during the process. Books 
should be set upright on tables, and opened as widely and freely as 
possible, so the leaves hang loose and separate. Engravings and 
paintings may be freely exposed by the removal of the glass-covering 
or other method to the action of the formaldehyde, and should in 
the case of paintings be sponged carefully with lukewarm water im- 
mediately after being exposed to the fumes of the formaldehyde. 
Corrosive sublimate is not to be used on metallic articles, or of those 
of marble or other lime salt; these substances are not, however, 
affected by formaldehyde. The cleaning of the room after 
disinfection should be extremely thorough. 

Prisons, hospital-wards, houses which have been inhabited by 
tuberculous patients, and other edifices, are liable to become so 
infected with organisms, especially with tubercular organisms, that 
the processes detailed are not sufficient. Frequently such buildings 
are more or less out of repair; when this is the case, all decomposed 
wood should be torn out and left out during the process of disinfection. 
(See below.) Moreover, not rarely in these buildings the most rigid 
disinfection will fail to destroy germs which work their waj' into 
absorbent walls or wood surfaces or deep crevices, so that scraping 
off of the plaster and tearing out of the rooms may be necessary for 
the purification of the apartment. If the germs are active, as are 
those of typhus fever, in order to protect the workmen, a superficial 
disinfection should precede these destructive acts. In many of these 
cases the first stage of disinfection should consist of a free application, 
by means of mops, of a four-per-cent. solution of sodium hydroxide 
to ceilings, walls, surbases, floors, sinks, drains. Such a hot alkaline 
solution acts very decidedly upon the germs themselves and rapidly 
destroys all kinds of filth, and thereby exposes the germs to the 
after-action of more generally recognized germicides. A day or two 
after the use of the soda the apartment should be thoroughly washed 
out with plain warm water. When there are wide cracks or crevices, 
corrosive sublimate solution,* 1:200, should be freely used before 
the alkaline solution, which will decompose and render innocuous 

* In this, as in many other cases, when there is danger of corrosive sublimate being decom- 
posed by organic or alkaline substances, the solution is made more effective by the use of hydro- 
chloric acid. Half an ounce of mercuric chloride, two ounces of strong hydrochloric acid, and 
three gallons of water, make a very effective solution, not so readily decomposed as the simple 
mercuric chloride. 



DISINFECTANTS 70S 

any excess of the nun-curie chloride. Whenever there is a metal 
surface, such as occurs in sinks, drains, pipes, etc., a five-per- 
cent, cresol solution is preferable to the corrosive sublimate; 
or a ten-per-cent. solution of formaldehyde may be used. After the 
processes spoken of have been carried out, the final disinfection may 
be made by mopping out with large quantities of the Formaldehyde 
solution; or in some instances chlorinated or formaldehyde lime- 
wash, as detailed below, is preferable. 

Formaldehyde vapor is often used, but is less effective than the 
application in mass of formaldehyde solution to the various surfaces. 

Infected stables offer problems different from those of ordinary 
buildings; the tetanus germ exists in the soil, and when the infection 
of the stable is with this bacillus, the removal of the animals to another 
locality and the torch are almost the only resource. The products 
of animal and vegetable decomposition are so abundant about stables 
that corrosive sublimate is of very little use, except for washing off 
mangers and similar objects. Further, in the case of dairy stables, 
phenol, chlorine, and other disinfectants which have strong and per- 
sistent odors, cannot well be employed because they are liable to 
damage the milk for a long time after their use. The first step in the 
disinfection of a stable is the removal and destruction of all rubbish, 
loose boards, and decomposed wood. Then the absolute cleaning-up 
of the stable with a solution of sodium carbonate. Floor, walls, 
ceiling, wood-work of the stable should finally be deluged with lime- 
wash containing chlorinated lime, or formaldehyde solution. The 
chlorinated lime is cheap and equally effective with the formalde- 
hyde when there is no special objection to its use. From six to eight 
ounces of the chlorinated lime may be added to each gallon of lime- 
wash; or the official formaldehyde solution may be used in the pro- 
portion of 1 : 30 to 1 : 20. Hay, straw 7 , manure, and the general refuse of 
an infected stable may be burned, or preserved for use as a fertilizer by 
mixing with chlorinated lime and allowing to stand for some weeks. 

In all cases of disinfection success depends upon the thoroughness 
with which the process is carried out. 

The following table has been compiled by H. C. Wood, Jr., show- 
ing the solutions of various germicides equivalent to a 1 : 2000 or a 
1:10,000 corrosive sublimate solution: 

Mercury bichloride . . 1 : 2000 1 : 10,000 Creosote 1 : 100 

Mercury biniodide . . 1:3000 1:15,000 Sulphuric acid 1:100 

Silver nitrate 1 : 400 1 : 4000 Sulphurous acid 1 : 50 

Chlorinated lime 1:100 1:1000 Sodium hydrate 1:100 

Formaldehyde 1:50 1:150 Solution of chlorinated soda 1:50 

Lvsol 1 : 40 1 : 150 Phenol sodique 1 : 25 

Phenol 1 : 30 1 : 100 Piatt's chlorides 1: 20 

Creolin 1:5 1:75 Water of hydrogen dioxide 

Iodine 1:500 (U. S. P.) 1:3 

Salicylic acid 1 : 150 Alcohol 1:3 

Cupric sulphate 1 : 200 Listerine pure 

Thymol 1 : 150 Volatile oils pure 

Potassium permanganate 1 : 100 Ichthyol pure 



704 



EXTRANEOUS REMEDIES 



REFERENCES. 



HEAT. 



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Ueitsamte, i. 
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Fliesbuhg. 



Fit ANKENBURGER 

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Schmidt 

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Stone 

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Tauber 

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Turtschaninow 

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Wallace. . 

Wilson. . . . 



Wood, Jr. 



DISINFECTANTS 



7 or, 



REFERENCES {Continued). 



GUAIACOL. 



Eschle S. Jh.. 1896, col. 

Gotnard B. G. T.. 1893. 

Hatch M. News, 1003, lxxxiii. 

!>. M. \\ .. I SOS. 

Kvprianow Centralb. f. Bakter., 1894, 

xv. 
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CRESOL. 

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Dresden, 1895-98. 

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Pfreuger A. Pharm., 1890, 701 . 

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1904, vi. 427. 

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Van Ermengen.. B. A. R. B., 1889, iii. GO. 
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NAPHTHOL. 

Sahli Th. M., 1887. 

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113. 



MENTHOL. 

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THYMOL. 

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Bishop. 



Goldscheider. 

Iotf.yko 

Pellacani. . . . 
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Balz 

Blum 

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Henry 

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TlJNNlri.ll'll. Mini Komi mii iu Cl>. |'., 1001, 
xv. 2. 

VanErmengin and Suo(i \ .I'Ikiiiii., I S'.l.'i, i. 

Zohn M. M. W., IflOO, ii. 

Ii. M. .1., 1908, i. 

Ii. M. .1., 1902. ii. 



AslIURST . . . 

Bucholz . . . 
Dougai.l. . . 
Fleck 



Gauuod. 
Grtjbjb. . 
Keller. 



Lewandosky. 
Meissnek and 



Salkowski. . . 
Seligsohn. . . 
Senator 



Ure 

VlRCHOW. 



BENZOIN. 

.. .P. M. J., Feb. 24, 1900. 

A. E. 1'. P., iv. 
. M. T. G., 1872, i. 
. . . Benzoesilure, etc, Munich, 

1875. 
. . .L. L., Nov. 1844. 
. .Cb. C, 1870, 777. 
...Ann. der Clicin. u. Pharm., 

1842, xliii. 
.. .Z. K. M., 1903, xl. 
Shepard. .Untersuch. iiber das 

Entstehen der Hippur- 

siiuro, Hanover, 1866. 
...B. K. W., 1875, 297. 
. . .Chem. Centralb., 1861. 
. . .Allg. Wien. Med. Zeitung, 

1876, xxiii. 
. . M. C. Tr., 1841, xxix. 30. 
. . . Z. P. C, vi. 



Landerer. . . 
Robinson. . . 



CINNAMIC ACID. 

.M. M. W., xxxv. 
.M. A., 1902. 



SULPHUROUS ACID. 

Pfeiffer Sajous's Annual, 1891. 

OXALIC ACID. 

Kelly Amer. Journ. Obstetrics, 

1891, xxiv. 
Kobert and Kussner. .V. A. P. A., lxxvii. 

109. 
Loew Sitzb. d. Gesellsch. f. Mor- 

phol. und Physiol., 1892, 

viii. 

Rabuteau Gazette Mdd., 1874, 92. 

Taylor Med. Jurisprud- i. 224. 

BORIC ACID. 

Andrews Chicago Med. Exam., 1889, 

lviii. 

Bucholz A. E. P. P., iv. 

Chittenden and Gies. .A. J. P., i. 39. 
Dujardin Union Mdd. du Nord-Est, 

Nov. 1891. 
Dumas and Schnatzles. .Pharm. Journ., 

April, 1874. 

Fere Semaine Mdd., 1894, xiv. 

Folsom B. M. S. J., Feb. 18, 1886. 

Greene B. M. S. J., ciii. 209. 

Gruber H. S. Jb., 1879. 

Harrington A. J. M. S., exxviii. 418. 

Hogner S. Jb., ccii. 

Maass Th. M., 1903, iii. 

Mododewkow St. L. C. R., 1881. 

Plaut Thesis, Wurzburg, 1889. 

Rosenthal Allg. Wien. Med. Ztg., Jan. 

1884. 

Sternberg A. J. M. S., lxxxiv. 321. 

Straub S. Jb., 280. 

Walb C. K. M., 1882, iii. 529. 

Welch N. Y. M. R., 1888, xxxiv. 

PRACTICAL DISINFECTION. 

Abbott Tr. I. C. C, 1893. 



45 



APPENDIX. 



APOTHECARIES' WEIGHT-APOTHECARIES' MEASURE. 



Pound, 

Ounce, S 

Drachm, 5 

Scruple, 3 

Grain, gr 



FORMERLY OFFICIAL IN THE ONITED STATES PHARMACOPOEIA. 



lb = 



12 Ounces. 

8 Drachms. 

3 Scruples. 
20 Grains. 

1 Grain. 



Gallon, . C 

Pint, O 

Fluidounce, f3 

Fluidrachm, f5 

Minim, III 



8 Pints. 
16 Fluidounces. 

8 Fluidrachms 
60 Minims. 

1 Minim. 



WEIGHTS AND MEASURES OF THE METRIC OR FRENCH SYSTEM. 

NOW OFFICIAL IN THE UNITED STATES PHARMACOPOEIA. 



MEASURES OF LENGTH. 

One Myriametre = 10,000 Metres. 

One Kilometre = 1,000 Metres. 

One Hectometre = 100 Metres. 

One Decametre = 10 Metres. 

One METRE = the ten-millionth part of a quarter of the meridian of the earth. 

One Decimetre = the tenth part of one Metre or 0.1 Metre. 

One Centimetre = the hundredth part of one Metre, or 0.01 Metre; written Cm. 

One Millimetre = the thousandth part of one Metre, or 0.001 Metre; written Mm. 



One Myriagramme 
One Kilogramme 
One Hectogramme 
One Decagramme 
One GRAMME 
One Decigramme 
One Centigramme 
One Milligramme 



WEIGHTS. 
10,000 Grammes. 
1,000 Grammes. 
100 Grammes. 
10 Grammes. 
the weight of a cubic Centimetre of Water at 4° C; written Gm. 
the tenth part of one Gramme, or 0.1 Gramme, 
the hundredth part of one Gramme, or 0.01 Gramme, 
the thousandth part of one Gramme, or 0.001 Gramme. 



MEASURES OF CAPACITY. 

One Myrialitre = 10 cubic Metres, or the measure of 10 Milliers of Water. 

One Kilolitre = 1 cubic Metre, or the measure of 1 Millier of Water. 

One Hectolitre = 100 cubic Decimetres, or the measure of 1 Quintal of Water. 

One Decalitre = 10 cubic Decimetres, or the measure of 1 Myriagramme of Water. 

One LITRE = 1 cubic Decimetre, or the measure of 1 Kilogramme of Water. 

One Decilitre = 100 cubic Centimetres, or the measure of 1 Hectogramme of Water. 

One Centilitre = 10 cubic Centimetres, or the measure of 1 Decagramme of Water. 

One Millitre = 1 cubic Centimetre, or the measure of 1 Gramme of Water. 
706 



APPENDIX 



707 



RELATION OF APOTHECARIES' WEIGHTS AND MEASURES 
TO EACH OTHER. 



One l'minil 
One Ounoe 
One Drachm 
One Scruple 
One Grain 
One Gallon 
Oue Pint 
One Fluidounce 
One Fluidrachm 
One Minim 



In diatittad water eri the temperature of 60° 
0.7900031 Pint 
1.0533370 Fluidounees 
1.0533370 Fluidraohms 



10.1265427 Pounds 
1.2658178 Pounds 
0.9493633 Ounce 
0.9493633 Drachm 



0007.2238 

505.8019 

63.2002 

21.0007 

1.0533 

5.S32.S.SS02 

7291.1107 

455.0944 

50.9018 

0.9493 



Minima, 

Minims. 

Minims. 

Minims. 

Minims. 

Grains, 

drains. 

Grains, 
Grains, 

Grain. 



RELATION OF APOTHECARIES' OR WINE MEASURE 
TO CUBIC MEASURE. 



One Gallon 

One Pint 

One Fluidounce 



231. Cubic Inches. 

28.875 Cubic Inches. 

1.80468 Cubic Inches. 



One Fluidrachm 
One Minim 



0.22558 Cubic Inch 
0.00375 Cubic Inch, 



RELATION OF APOTHECARIES' WEIGHTS TO METRICAL WEIGHTS. 



Fraction of a groin in 
Milligrammes. 



Grains in equivalent metrical 
weights. 



Drachms, Ounces, and Pounds in 
equivalent metrical weights. 



Grain. 




Milligrammes. 


Grains. 




Centigrammes. 


1 Drachms. 




Grammes. 


..'■ 


= 


1.012 


1 


= 


6.479 


1 


= 


3.887 




= 


1.079 






Decigrammes. 


2 


= 


7.775 


A 


= 


1.295 


2 


= 


1.295 






Decagrammes 


1 

IS 


= 


1.349 


3 


= 


1.943 


3 


= 


1.166 


A 


= 


1.619 


4 


= 


2.591 


4 


= 


1.555 


i 
38 


= 


1.799 
2.159 


5 



_ 


3.239 
3.887 


5 
6 


= 


1.943 
2.332 

2.721 


A 


= 


2.591 


7 


= 


4.535 


Ounces. 






,\ 


= 


2.699 


8 


= 


5.183 


1 


= 


3.1103 


■ 


= 


3.239 


9 


= 


5.831 


'2 


= 


0.2206 


i 


= 


4.049 


10 


= 


0.479 


3 


= 


9.3309 


1 

1 S 


= 


4.319 


12 


_ 


7.775 






Hectogrammes 


1» 


= 


5.399 
0.479 


15 


= 


9.798 
Grammes. 


4 
5 
6 


= 


1.2441 
1.5551 
1.8661 


\ 


= 


8.098 


16 


= 


1.036 


7 


= 


2.1772 


1 


= 


10.798 


20 


= 


1.295 


8 


= 


2.4882 


i 


= 


12.958 


24 


= 


1.555 


9 


= 


2.7992 


1 


= 


16.197 


25 


= 


1.619 


10 


= 


3.1103 


i 


= 


21.597 


30 


= 


1.943 


11 


= 


3.4213 


5 


= 


32.395 


40 


= 


2.591 


Pounds. 












50 


= 


3.239 


1 


- 


.1.7324 






, 


60 


= 


3.887 

i 


3 




7.4648 

Kilogrammes. 

1.1197 



708 



APPENDIX 



RELATION OF METRICAL WEIGHTS TO APOTHECARIES' WEIGHTS. 



Metrical 
Weights. 




Exact 
equivalents 


A pproximate 
equivalents in 


Metrical 
Weights. 


Exact 
equivalents 


Approximate 
equivalents in 






in grains. 


grains. 






in grains. 


Troy Weight. 


Milligrammes. 






Grammes 








1 


= 


.0154 


& 


1 


= 


15.434 


gr. xv. 


2 


= 


.0308 


A 


2 


= 


30.868 


5ss. 


3 


— 


.0463 


A 


3 


= 


46.302 


3ij. 


4 


_ 


.0617 


A 


4 


= 


61.736 


Si. 


5 


._ 


.0771 


A 


5 


= 


77.170 


3iv. 


6 

7 


= 


.0926 
.1080 


ft 

.1 

B 


6 

8 


= 


92.604 
108.038 
123.472 


5iss. 

3vss. 
Sij. 


8 


= 


.1234 


X 


9 


= 


138.906 


3vij. 


9 


= 


.1389 


l 

7 


Decagrammes 






Centigramm 


es. 






1 


= 


154.340 


Siiss. 


1 


= 


.1543 


i^ 


2 


= 


308.680 


5v. 


2 


= 


.3086 


i 


3 


= 


463.020 


Sviiss. 


3 


= 


.4630 


T3 


4 


= 


617.360 


Sx. 


4 


= 


.6173 


7 
IT 


5 


= 


771.701 


3xiij. 


5 




.7717 


J 


6 


= 


926.041 


Sxv. 


6 


_ 


.9260 


ft 


7 


= 


1,080.381 


Sxviij. 




_ 


1.0803 


1 


8 


= 


1,234.721 


Sxx. 


8 


= 


1.2347 


a 


9 = 

Hectogrammes. 


1,389.062 


Sxxiij. 


9 


= 


1.3890 


n 


1 


= 


1,543.402 


Siii 9v. 


Decigrammes. 






2 


= 


3,086.804 


Svj Siij. 


1 


= 


1.543 


n 


3 


= 


4,630.206 


Six Sv. 


2 


= 


3.086 


3 


4 


= 


6,173.609 


Ibi Svij. 


3 


= 


4.630 


H 


5 


= 


7,717.011 


lt>i Siv. 


4 


= 


6.173 


6 


6 


= 


9,260.413 


Ibi Svij. 


5 


= 


7.717 


~1 


7 


= 


10,803.816 


Ibi Sx Siv. 


6 


= 


9.260 


9 


8 


= 


12,347.218 


Ibij Si Sv. 


7 


= 


10.803 


11 


9 


= 


13,890.620 


Ibij Sv. 


8 


_ 


12.347 


12J 


Kilogramme. 






9 


= 


13.890 


14 


1 = 
Myriagramme. 


15,434.574 


Ibij. Sviij. 










1 


= 


154,340.23 


f lb xxvi. 
\ Six Siv. 












APPENDIX 



709 



TABLE OF THE PROPORTION BY MEASURE OF ALCOHOL (SP. GR. 

0.825) CONTAINED IN ONE HUNDRED PARTS OF 

DIFFERENT WINES, ETC.* 



Lisa (mean) L'.V II 

Raisin wine (mean).. '-'•">. l- 

Marsala [Sicily ma- 
deira] (mean I . . 2,'>.09 

strongest t,J.) 21.10 

weakest (.J.) 19.90 

Port, strongest. . ■_V ) ..s:i 

mean 22.90 

weakest 39.00 

strongest (C.).. • . 20.49 

mean (C.) 18.08 

weakest (C.) 10.80 

strongest (J.) 23.20 

weakest (J.) 20.70 

White port (C.) 17.22 

Madeira, strongest 24.42 

mean 22.27 

weakest 19.24 

strongest (C.) 20.35 

strongest (J.) 19.70 

weakest (J.) 19.00 

Sercial madeira 21.40 

Ditto (C.) 18.50 

Sherry, strongest 19.81 

mean 19.17 

weakest 18.25 

strongest (C.) 19.31 

mean (C.) 18.47 

weakest (C.) 10.90 

Amontillado (C.) . . 15.18 

strongest (J.) 24.70 

weakest (J.) 15.40 



TenerifTo 19.79 

Toneriffe (C.) . . 16.01 

Colares 19.75 

Lachryma Christ i 19.70 

White Constantia 19.75 

Red Constantia 18.92 

Lisbon 18.94 

Ditto (C.) 19.09 

Bucellas 18.49 

Red madeira (mean).. . 20.35 

Cape muscat 18.25 

Cape madeira (mean) . 20.51 

Grape wine 18.11 

Calcavella (mean) 18.65 

Vidonia 19.25 

Alba flora 17.26 

Zante 17.05 

Malaga 17.26 

White Hermitage 17.43 

Roussillon (mean) 18.13 

Claret (strongest) 17.11 

mean 15.10 

weakest 12.91 

ditto (F.) 14.73 

vin-ordinaire (C.) . 10.42 
Ch&teau-Latour, 

1825 (C.) 9.38 

first-growth, 1811 

(C.) 9.32 

strongest (J.) 11.10 

weakest (J.) 9.10 

Malmsey madeira 16.40 

Ditto (C.) 15.00 













. 15.52 


Ditto (C.) 






. . 15.28 


Sauterne 




Burgundy (mean). . . 


. . 14.57 


strongest (J.) . . . 


. . 13.20 




.. 10.10 




. . 12.08 




. . 13.00 


weakest (J.) .... 


. . 9.50 




. 14.63 




. 13.86 


Tont 


. . 13.30 


Champagne (mean). . 


. . 12.61 


Ditto (F.) 


. 12.20 


Ditto, strongest (J.) . 


. . 14.80 




. 14.10 




. 12.32 


Vin de Grave (mean) 


.. 13.37 


Frontignac (Rives 




Altes) 


. 12.79 


Ditto (C.) 


. 12.29 


Cflte rotie 


12.32 


Tokay 


9 88 


Rudesheimer, first 




quality (C). . . 


. 10.14 




. 8.35 


Hambacher, first 






. 8.88 


Catawba (Stearns) . . 


.8 to 11 



Cider, highest average . 9.87 
lowest average .... 5.21 
Perry, average of four 

samples 7.26 

Mead 7.32 

Ale (Burton) 8.88 



Ale (Edinburgh) 6.20 

Ale (Dorchester) 5.56 

Brown stout 6.80 

London porter 4.20 

London small beer 1.28 



Brandy 53.39 

Rum 53.68 

Gin 51.00 

Scotch whisky 54.32 

Irish whisky 53.90 



* The analyses whose results are given in this table were mostly made by Mr. Brande. When 
no mark is attached, the quotation is upon his authority. WTien the mark (F.) is added, the 
analysis was made by Julia- Fontenelle; (C), by Professor Christson; (J.), by Dr. H. Bence Jones. 



INDEX OF DISEASES 



Abscess : 

alcohol, to support system by its food value, also as heart stimulant, 204 

bismuth oxyioaogallate, glycerin solution injected into cold abscesses, 307. 

boric acid, a feeble antiseptic, 69N. 

formaldehyde, employed in tuberculous cases, 689. 

hydrogen dioxide, as a disinfectant and cleansing agent, 662. 

iodoform, in tuberculous forms, 384. 

menthol, a sat mated alcoholic solution painted on superficial abscesses, 682. 

opsonic treatment, 415. 

papain, to destroy surrounding membranes in old abscesses, 651. 

potassium permanganate, as a cleansing disinfectant when fetid discharges, 660. 

tannic acid, when excessive secretion, 286. 

Acidity of Stomach : 

ammonia, stimulant, promptly acting, too irritating to be used in inflammatory 

conditions, 1S6. 
magnesia, antacid and gently laxative, 635. 
soda, the most generally serviceable antacid, 634. 

Acne: 

arsenic, valuable alterative, especially in chronic cases, 351. 

calcium sulphide, credited with peculiar alterative action, 694. 

ichthyol, supposed to possess the power of penetrating the skin and exercising a 

local alterative action, 396. 
iodine, powerfully antiseptic but of doubtful value, 378. 
oil of cajuput, stimulant and parasiticide, 442. 
opsonic treatment, 415. 

phosphorus, used internally in cases with poor nutrition, 340. 
solution of mercuric nitrate, caustic, used to destroy pustules, 614. 

Aconite Poisoning : 

alcohol, a rapidly acting cardiac stimulant, 204. 

digitalis, a powerful stimulant to the heart, but slowly acting, 231. 

Treatment of, 275. 

Actinomycosis : 

potassium iodide, only drug likely to be of service internally, 377. 

Addison's Disease : 

suprarenal capsule, supplies lacking secretions, use must be continued indefi- 
nitely, 24.5. 

Ague: 

See Malaria. 

Alcoholism : 

apomorphine, emetic and sedative, 495. 
capsicum, for alcoholic gastritis, 483. 

gold and sodium chloride, supposed to exercise a specific effect on central ner- 
vous system in alcoholic habit, but probably valueless, 373. 
strychnine, valuable in chronic alcoholism, 140. 
treatment of acute alcoholism, 208. 
See also Delirium Tremens. 

Alopecia : 

arsenic, in atrophic variety, 351. 
pilocarpine, 567. 

711 









712 INDEX OF DISEASES 

Amaurosis : 

See Blindness. 

Amblyopia : 

strychnine, especially useful in tobacco or alcoholic cases, 138. 

Amenorrhea : 

aloes, cathartic, tends to increase pelvic congestion, enters into several emmena- 

gogue combinations, 506. 
apiol, to be given for a week previous to expected menses, 580. 
clove tea, useful where menses are suppressed by "cold," 481. 
cotton root, stimulant to uterus, 598. 
diaphoretics, of service in acute suppressions, 561. 
emmenagogues, their limitations and uses, 579 
ginger, may be given in form of infusion, 482. 
oxalic acid, active but somewhat dangerous, 686. 

potassium permanganate, not very valuable, but sometimes of service, 581. 
santonin, has been recommended in acute menstrual suppression, 640. 
sumbul, useful in cases associated with nervous symptoms, 17. 
turpentine, when there is much relaxation, 551. 

Ammonia Poisoning: 

treatment, 282. 

Ammoniacal Urine: 

See Cystitis. 

Ankylostomiasis : 

See Uncinariasis. 

Anaemia : 

See Chlorosis and Pernicious Anaemia. 

Anaesthesia, Accidents in : 

ammonia, rapidly acting heart stimulant, 185. 
artificial respiration, a most important factor, 48. 
cardiac massage, may be tried in desperate cases, 46. 
treatment of, 46. 

Aneurism : 

digitalis, useful where heart is very feeble, but must be employed with great 

caution on account of danger of rupture, 229. 
gelatin, promotes coagulation of the blood, 401. 
potassium iodide, largely employed, but there is no explanation of the manner 

in which it benefits, 377. 

Angina : 

See Sore Throat. 

Angina Pectoris : 

amyl nitrite, very prompt and efficacious, to be used during the attack, 168. 
erythrol tetranitrate, acts like nitroglycerin but more lasting, 170. 

Anorexia : 

bitters, stimulate the flow of gastric juice, also probably increase appetite through 

their bitter taste, 475. 
orexine, a synthetic bitter, highly lauded, 478. 
quinine, acts as a bitter, but also has effect on metabolism, 429. 
strychnine, 138. 

Anthrax : 

plienol, to be injected into the ulcer, 669. 

Aortic Lesions: 

See Endocarditis. 



INDEX Or DISEASES 713 

Aphthous Stomatitis : 

See S ton \ nns. 

Apoplexy : 

rroton oil, useful as a purgative where patient cannot swallow; also acts as 

revulsant. 522, 
emetics, not useful in true apoplexy, bul in those forms of coma resembling 

apoplexy, int. 

nitroglycerin, useful to avert threatened apoplexy by dilating the blood-vessels, 
169. 

Arsenic Poisoning: 

/erric hydroxide, this, the best chemical antidote, may be prepared extempo- 
raneously by adding any alkali to a solution of ferric sulphate or chloride, 328. 
treatment, 355. 

Arteriosclerosis : 

digitalis, if heart is weak, 229. 

nitrites, to lower pressure by dilating blood-vessels, 169. 

Ascites : 

See Dropsy. 

Asthenopia : 

strychnine, acts almost specifically, 139. 

Asthma : 

Symptomatic Treatment: 

amyl nitrite, very prompt and powerful, used by inhalation during attack, 169. 

anaesthetics, sometimes useful during attack, 22. 

atropine, may be given hypodermically in large doses, probably less useful 

than the burning belladonna, 104. 
belladonna, useful, especially to be burned and vapors inluiled, 104. 
chloral, occasionally but not generally useful, 80. 

chloral jormamid, recommended in asthma depending upon cardiac disease, 90. 
compound arsenical paper formula for a compound to be smoked, (note) 572. 
emetics, 487. 
dionine, 73. 
gelsemium, 173. 

grindelia, useful as an expectorant, may be added to a burning powder, 576. 
heroin, especially useful in secondary asthma, acts by lessening irritability of 

respiratory centers, 75. 
lobelia, may be used as an expectorant, also in emetic doses during paroxysms, 

171. 
nitroglycerin, may be used hypodermically in the place of amyl nitrite. 
Constitutional Treatment: 

antipyrine, lessens irritability of nervous system, 463. 

arsenic, may be used either locally or internally, 351. 

aspidosperma, acts upon respiratory center, 178. 

atropine, may be used as a preventative of spasmodic asthma, 104. 

hyoscine, similar to atropine in its effect, more sedative, 111. 

potassium iodide, one of the most valuable drugs known between the paroxysms, 

376. 
pyramidon, 472. 

spartein, may be employed in asthma depending upon cardiac lesions, 250. 
suprarenal capsules, recommended to be used internally, 246. 

Atropine Poisoning : 

pilocarpine, physiological antagonist to atropine, 568. 
treatment of, 108. 

Belladonna Poisoning : 

See Atropine Poisoning. 



714 INDEX OF DISEASES 

Biliousness : 

emetics, mechanically relieve portal congestions, 487. 

ipecacuanha, has a special action on the liver, 491. 

mercury, in the form of calomel or blue-mass, the most generally valuable remedy 

in act ue cases, 515. 
nitro-hydrochloric acid, of service especially in chronic cases, 333. 
oxgall, is the most powerful stimulant to hepatic secretion known, 508. 
podophyllum, sometimes called "vegetable mercury" on account of its effect 

on the liver, 518. 
potassium acetate and citrate, of service in chronic biliousness, 538. 

Bites : 

See Hydrophobia, also Snake-bites. 
Black-water Fever : 

methylene-blue, is destructive to malarial parasite, but not irritant to the kidney, 
439. 

Bladder, Irritable : 

See Cystitis. 

Blindness : 

santonin, 640. 

strychnine, especially useful in toxic cases as alcohol or tobacco, 138. 

Boils : 

calcium sulphide, useful where successive crops of boils, 694. 

infiltration anesthesia, to open boils, 53. 

menthol, saturated alcoholic solution painted over area will sometimes abort., 682. 

opsonic treatment, 415. 

phosphorus, as general tonic "and alterative, 340. 

Bone Diseases : 

iodine, internally in scrofulous cases, 376. 

phenol, injected deeply, 669. 

phospliorus, has a stimulant action on growth of bone, 340. 

Brain Softening: 

pliosphorus, sometimes of benefit, 340. 

Bright' s Disease : 

antipyrine, 464. 

apocynum, to eliminate dropsical effusions, 237. 

caffeine, to evacuate dropsy, to be used only very cautiously if at all in acute 

cases, 217. 
calomel, one of the most powerful diuretics known, 530. 

diaphoretics, aid in the excretion of waste products through the skin, 562. 
gallic acid, to diminish excessive secretion in chronic interstitial nephritis, 287. 
hypodermoclysis, in acute irritation of kidneys or suppression, 526. 
pilocarpine, may be used to produce sweating, also to stimulate kidney in acute 

suppression, 567. 
potassium bitartrate, of value in acute nephritis, 539. 
strontium lactate, claimed to diminish the amount of albumin, but of doubtful 

value, 545. 
strophanthus, more stimulant to kidneys than digitalis, 241. 
tannalbin, in cases where large amounts of albumin, 289. 
theobromine, may be employed in both acute and chronic cases when secretion 

is insufficient, 532. 
theocin, a synthetic alkaloid of value in dropsical cases, 532. 
thyroid extract, 496. 

tincture of ferric chloride, much employed in chronic cases, 328. 
water, in acute irritations large draughts of water often valuable, 526. 

Bronchitis, Acute : 

ammonium chloride, somewhat stimulant, use after secretion is established, 185. 
antimony, to be employed only in robust or sthenic patients, 260. 
apomorphine hydrochloride, encourages the establishment of secretion, 495. 



index or Diseases n.-, 

Bronchitis, Acute (Continued): 
codeine, as a oough sedative, 72. 

demulcents, 111 7. 

eucalyptus, used when there is free Beeretion, 1 12. 

heroine, a very valuable cough sedative, 75, 

ipecacuanha, inn-ease- expectoration, use in early stages 573. 

licorice, 019. 

lobelia, of service when there is tendency to asthmatic spasms, 171. 

oU of sandal-wood, in the latter stages, 555. 

opium, cough sedative, avoid where expectoration is profuse, 65. 

pot08Stum citrate, increases secretion, especially serviceable in early stages 57:i 

senega, 57 I. ' 

Steam atomizer, method of using, 572. 

sulphuretted hydrogen, useful where free expectoration, 57X. 

tar, used only in advanced stages, 576. 

terebene, stimulating expectorant, use in later stages, 575. 

terpin hydrate, of service after secretion has been established, 575. 

turpentine stu/>es, act by counter-irritation, 550. 

Bronchitis, Chronic: 

ammoniac, 577. , 

ammonium chloride, employed where expectoration is not profuse, 185. 

arsenic, may be used either internally or in form of cigarettes, 351. 

asafetida, of service in the aged, 17. 

aspidosperma, to relieve dyspnoea, 180. 

balsam of Tolu, 577. 

benzoic acid, a valuable remedy, 692. 

Burgundy pitch, externally as a counter-irritant, 610. 

cimicifuga, 19. 

copaiba, in cases with free muco-purulent expectoration, 553. 

creosote, one of the most active stimulating expectorants, 675. 

creosote carbonate, supposed to be less irritating to the stomach than creosote 

670. 
eucalyptus, an active stimulant expectorant, 442. 
formaldehyde, inhalations of, 689. 
grindelia, relaxes spasm of bronchial muscles and stimulates mucous membranes 

576. 
naphthalin, when free expectoration, 680. 
oil of sandal-wood, a useful stimulant expectorant, 555. 
oil of turpentine, 551 . 

physostigma, when there is weakness of bronchial muscles, 151. 
strychnine, as a stimulant in the feeble to aid expulsion of secretion, 139. 
sulphuretted hydrogen, an unpleasant but active remedy especially where purulent 

expectoration, 578. 
tar, a useful remedy best employed in form of syrup, 576. 
terbene, an active stimulating expectorant, 575. 
terpin hydrate, a very useful drug in cases of mild type, 575. 
theocol, 678. 

Bronchorrhcea : 

atomization, as a means of applying remedies locally, 572. 
gallic add, an internal astringent, 287. 

Bruises : 

arnica, 610. 

camphor, 191. 

ichthyol, 396. 

solution of lead subacetate, sedative and astringent embrocation, 294. 

vinegar, a useful external application, 290. 

Buboes : 

chloral, in solution forms a stimulant and antiseptic wash, SO. 
phenol, deep injections of, 669. 

Bubonic Plague : 

serum treatment, useful as prophylactic as well as curative, 412. 



716 INDEX OF DISEASES 

Burns: 

aluminum hydroxide, mildly astringent and protective, 292. 

boric acid, as a mildly antiseptic dressing, 698. 

Carron oil, a soothing local application, 637. 

chalk, offers a desiccant protective dusting powder, 637. 

creosote, recommended when there is excessive granulation, 676. 

hot baths, to combat the collapse, 560. 

ichthyol, 396. 

iodoform, analgesic, desiccant, and antiseptic, 382. 

lead carbonate, in the form of ointment is a sedative astringent, use with care, 294. 

orthoform, local anaesthetic and antiseptic, 52. 

phenol, anesthetic and germicidal, 669. 

treatment of, (note) 382. 

volatile oils, (note) 479. 

Bursitis : 

phenol, deeply injected, 669 

Cachexia : 

cod-liver oil, appears to have specific influence on nutrition, 390. 
glycerin, 626. 

Calculi : 

anaesthetics, to alleviate pain and produce relaxation during passage of stone, 22. 

atropine, to relieve spasm, 104. 

benzoic acid, in uric acid calculi, supposed to check elimination of uric acid, 692. 

olive oil, probably of some value in cholelithiasis, 622. 

piperazine, will not dissolve calculi, 543. 

potassium acetate, to check the further deposition of uric acid, 538. 

sodium salts, to lessen viscidity of bile in gall-stones, 634. 

Cancer : 

arsenic, as a caustic in inoperable cases, 613. 
chloral, locally anaesthetic and antiseptic, 80. 
cocaine, to relieve pain, apply locally, 126. 
escharotics, only to be used in inoperable cases, 611. 
formaldehyde, deodorant and germicidal, 689. 
iodoform, lessens pain and absorbs discharge, 382. 
methylene blue, 439. 
solution of mercuric nitrate, as a caustic, 614. 

Cancer of Stomach : 

bismuth subnitrate, to relieve pain and vomiting, 306. 
chloretone, local anaesthetic, 92. 

diastase, to digest food when gastric secretions fail, 650. 
malt, 650. 

Carbolic Acid Poisoning: 

treatment, 672. 

Carbuncle : 

menthol, paint saturated alcoholic solution over surface 682. 
opsonic treatment, 415. 

Cardiac Disease, Chronic: 

See Heart Disease. 

Cardiac Dropsy : 

See Dropsy. 

Cardialgia : 

antacids, correct hyperacidity, 631. 
charcoal, to absorb gases, 652. 

Cataract : 

phosphorus, 340. 



INDEX OF DISEASES 717 

Catarrh of Air Passages : 

bismuth subnitratc, sedative astringent tor local application in aoute oa e , 308 

benzoic unit, to be given internally in subacute and chronic cases, 692. 

amphoric acid, applied locally, 192. 

flaxseed, may be vised freely in the form of a decoction, 019. 

guaiacol, as a stimulant in chronic cases, 077. 

hydrastin, applied locally, 595. 

thymol iodide, dusted on the mucous membranes, 387. 

See also Bronchitis and Coryza. 

Catarrh of Bladder: 

See Cystitis. 

Catarrhal Jaundice : 

See Jaundice. 
Cerebral Congestion : 

cathartics, 500. 
ergot, 589. 

Cerebral Excitement: 

cathartics, act by revulsion, 500. 

potassium bromide, useful when condition is not inflammatory, 156. 

Cerebral Softening: 

See Brain Softening. 

Chancres and Chancroids : 

black wash, as a local application, 370. 

Canquoin's paste, contains zinc chloride, 614. 

corrosive sublimate, less useful than solution of mercuric nitrate but actively 

germicidal and somewhat caustic, 614. 
escharotics, 611. 

hydrogen dioxide, cleansing and germicidal, 662. 
nitric acid, should be applied with a glass rod, 332, 615. 
red mercuric oxide, may be used in powder form, 370. 
resorcin, apply as dusting powder, 685. 
solution of mercuric nitrate, actively caustic, 614. 
sulphuric acid, actively caustic, 330. 
yellow wash, 370. 

Chapped Hands, Lips, or Nipples : 

benzoic acid, stimulant and antiseptic, especially useful in the form of benzoin, 693. 

glycerin, 626. 

tannic acid, to harden tender nipples, 286. 

Chilblains : 

copaiba, 553. 
creosote, 676. 

Child-birth : 

See Labor. 

Chloral Poisoning : 

treatment of, 82. 

Chlorosis : 

bone marrow, 531. 

cacodylic acid, doubtful if it is of value, 359. 

cetrarin, 620. 

copper sulphate, an old remedy, recently revived in cases with amenorrhoea, 310. 

euquinine, 436. 

iron, almost a specific, 326. 

lecithin, probably of some value but less beneficial than iron, 399. 

Cholelithiasis : 

See Calculi. 



718 INDEX OF DISEASES 

Cholera Asiatica : 

acetozone, an active intestinal antiseptic, 663. 
ammonia, for the collapse, 185. 
antitoxin, especially for immunization, 411. 
camphor, to lessen the diarrhoea, 191. 
sulphuric acid, of value as a prophylactic, 330. 

Cholera Infantum : 

antipyrine, 464. 

bismuth subnitrate, one of the most useful remedies known, 306. 

creosote, of service on account of local anaesthetic as well as antiseptic action, 675. 

resorcinol, antiseptic, 684. 

rhubarb, purgative and astringent, 504. 

sodium phosphate, useful to clean out bowel and encourage flow of bile, 511. 

sulphuric acid, actively astringent, 330. 

Chordee : 

camphor, 191. 

sulphonal, asserted to act as a sexual sedative, 84. 

Chorea : 

antipyrine, has some effect as motor sedative, 462. 

apomorphine, has been recommended in acute cases, 495. 

arsenic, one of the most generally useful remedies, give Fowler's solution in 

increasing doses, 352. 
cacodylic acid, an arsenical preparation, 359. 
Calabar bean, 151. 

chloral, to temporarily control convulsions when violent, 79. 
cimicifuga, give in conjunction with iron, 19. 
conium, 178. 

euquinine, used like quinine, 436. 
quinine, efficacious when patient can take large enough quantities, stimulates 

spinal inhibitory center, 429. 
strychnine, if any value it is as general tonic, 138. 
sulphonal, 84. 
zinc oxide, 309. 

Chronic Intestinal Atony : 

Calabar bean, a stimulant to non-striated muscle fibre, 1.51. 

Chyluria : 

methylene-blue, 439. 

Cicatrices : 

thiosinamine, asserted to have the power of absorbing scar tissue, 398. 

Cirrhosis of the Liver : 

apocynum , to evacuate effusion, 237. 

nitro-hydrochloric acid, in early stages exercises a directly beneficial action on 

liver, 333. 
See also Dropsy. 

Cocaine=poisoning : 

treatment of, 127. 

Cocainism : 

treatment of, 129. 

Colchicum=poisoning : 

treatment of, 395. 

Cold, a General : 

alcohol, as a preventive, 206. 

diaphoretics, most efficacious treatment, 561. 

licorice, 619. 

See also Bronchitis and Coryza. 



INDEX OF DISEASES 719 

Colic : 
antacids, in conditions with hyperacidity 631 
aaafetida, in Batulenl colic, a 'useful stimulant to peristalsis 17 
atropine, useful id spasmodic colic, lot. 
ctijuput, 442. 

chloroform, anodyne and carminative, frequently very useful 34 
ether, mildly carminative, 29, 

ginger, actively carminative, useful in flatulenl colic 182 
opium, to allay irritation, 65. 

Colica Pictonum : 

alum, chemical antidote to lead, also claimed to act specifically 292 
belladonna, probably most useful drug in this condition, 101. 
bee also Lead-Poisoning. 

Colitis : 

castor oil, purgative and sedative to inflamed mucous membrane S22 

copper sulphat>\ occasionally useful, applied locally, 310. 

high emmata, best treatment; various drugs, as silver nitrate or potassium 

chlorate, may be thus locally applied, 501. 
magnesium sulphate, benefits by cleaning out the cause 510 
silver nitrate, probably the most generally useful local'application, 317. 
Collapse : 

ammonia, prompt but temporary heart stimulant, give hypodermically 185 

atropine, vaso-motor stimulant, especially useful in cases with subnormal tem- 
perature, 105. 

ca jf cine, sodium and caffeine benzoate for hypodermic use 217. 

counter-irritants, 603. 

digitalis, powerful but slow, may be given hypodermically, 230. 

ergot, slow in its effect, 5S9. 

ether, 30. 

hot baths, only efficient method of maintaining body temperature, 560. 

hypodermochjsis, of physiological salt solution one of most efficient means ot 
maintaining the circulation, 526. 

sodium carbonate, 634. 

suprarenal extract, very quick but fugacious, may be given intravenously, but a 
dangerous remedy, 245. 

Warburg's tincture, 436. 

Colliquative Sweats : 

See Night-sweats. 

Coma: 

emetics, 487. 

Comedo : 

arsenic, 351. 

Condylomata : 

chromic acid, caustic, 615. 
nitric acid, actively caustic, 615. 
phenol, mildly caustic, 669. 

Congestion of Brain : 

See Cerebral Congestion-. 

Congestion of Lungs : 

atropine, 104. 
ergot, 589. 

Congestion of Spinal Cord: 

ergot, .589. 

Conium = poisoning : 
treatment of, 179 






720 INDEX OF DISEASES 

Conjunctivitis : 

alum, in the form of alum curd, astringent, 292. 

betanaphtol, applied locally dissolved in olive oil, 681. 

boric acid, one of the best local applications, soothing and antiseptic, 698. 

citrine ointment, in chronic cases, 371. 

copper sulphate, used in the granular type, 310. 

ichthargan, may be topically applied in one per cent, solution, 320. 

largin, a modern silver preparation recommended in the form of gelatin tablets 
locally, 319. 

lithium, in gouty cases, 543. 

protargol, recommended especially in gonorrhceal cases, 321. 

silver nitrate, a standard and useful treatment, an active germicide and astrin- 
gent, 316. 

suprarenal extract, powerfully antagonizes the congestion, 245. 

yellow mercuric oxide, in chronic cases 371. 

Constipation : 

aloes, in atonic cases, especially when accompanied with amenorrhcea, 506. 

asafetida, as stimulant to the intestinal muscles, especially useful in the aged, 17. 

atropine, in cases due to spasmodic constriction of the bowel, 104. 

belladonna, prevents griping and increases laxative effects of cathartics, 104. 

calomel, most valuable drug in biliousness, not to be used habitually, 515. 

cascara sagrada, especially useful in chronic constipation, 507. 

castor oil, useful only in acute cases, 521. 

cathartics, 498. 

croton oil, probably most powerful purgative known used to revulse or when 
patients refuse to swallow, 522. 

diet, 502. . 

enemata, 500. 

Epsom salt, a prompt and efficient saline, 510. 

euonymus, 520. 

magnesia, antacid laxative, 635. 

manna, 503. 

physostigma, stimulant to intestinal muscles, useful in atonic cases, 151. 

podophyllum, supposed to act upon the liver, hence the name "vegetable mer- 
cury," 518. 

rhubarb, used in debilitated cases, 504. 

senna, a very efficient laxative when soft passages desired, 506. 

solution of magnesium citrate, useful on account of its agreeable flavor, 513. 

strychnine, when intestinal atony, 139. 

sulphur, 694. 

tamarind, a laxative fruit, 503. 

treatment of, 498. 

wahoo, in chronic cases with hepatic torpor, 520. 

Convulsions : 

amyl nitrite, the remedy when convulsions must be controlled immediately, 

quick and powerful but fugacious, 168. 
anaesthetics, when prompt action desired; chloroform the most efficacious, 22. 
asafetida, in hysterical cases, 17. 
camphor, of little value except in hysteria, 191. 
chloral hydrate, useful in all types of convulsions if severe enough to threaten life, 

80. 
emetics, when convulsions of gastric origin, 487. 
musk, 15. 

bromides, useful when a persistent action desired, 157. 
See also Epilepsy, Tetanus, etc. 

Copper-poisoning : 

treatment of, 311. 

Corneal Ulcer: 

atropine, rests the eye by paralyzing accommodation, 106. 
dionine, increases the lymphatic circulation in the eye, 74. 
largin, germicidal, 319. 
physostigmine, to limit the spread of ulcers, 152. 



INDEX OF DISEASES 721 

Corpulence : 

See Obesity. 

Corrosive Sublimate poisoning : 

treatment of, 372. 

Coryza : 

atropine, give internally in acute stage; it checks excessive secretion 106 

bismuth subnitrate, locally applied, soothing and protective, 306. 

cocaine, contracts the engorged vessels, 126. 

cubebs, as a snuff in not too acute conditions, 554. 

glycerin, locally, 620. 

uhthyol, a ten per cent, ointment locally, 396. 

mlipifrin, 472. 

Cough : 

atropine, when cough is of spasmodic character, 104. 

codeine, acts on respiratory center, 72. 

dionine, 73. 

gelsemium, when of nervous type, 173. 

heroine, one of most generally useful cough sedatives known, 75. 

opium, to be avoided when expectoration is profuse, 65. 

prussic acid, of little value, 280. 

treatment of, 570. 

Cretinism : 

thyroid extract, 405. 

Croup : 

emetics, to evacuate membrane or mucus, 487. 

expectorants, 571. 

glycerin, 626. 

ipecacuanha, emetic and expectorant, 491. 

lime-water, apply locally by means of an atomizer 637. 

Cystitis : 

arbutin, alterative diuretic, 547. 

benzoic acid, valuable urinary antiseptic, especially useful when ammoniacal 

mine, 693. 
benzosulphinide, as a urinary antiseptic, 627. 
betol, antiseptic, 681. 

boric acid, antiseptic, may be given by mouth or used to wash out bladder, 698. 
buchu, acts as sedative to inflamed mucous membrane, 546 
camphoric acid, 192. 
copaiba, in chronic cases, 553. 

flaxseed, infusion, sedative to mucous membrane, useful in acute cases, 619. 
grindelia, 577 . 

guaiacol, urinary antiseptic, 677. 
hexamethylenamine, one of the best urinary disinfectants, supposed to liberate 

formaldehyde in the bladder, 557. 
hippurate of lime and lithia, (note) 691. 
io'line, 378. 

juniper, in chronic cases, 555. 
mcthylene-blue, mildly antiseptic, 439. 
pareira, 547. 

resorcinol, a three per cent, solution employed to irrigate the bladder, fix"). 
salicylic acid, rarely used to-day, 452. 
silver citrate, as local application to bladder 319. 
terebene, stimulant alterative diuretic, 575. 
terpin hydrate, 575. 

triticum, sedative to cystic mucous membrane, 548. 
turpentine, in chronic cases, 551. 
uva ursi, a valuable sedative alterative diuretic, 547. 
water, dilutes irritating urine, 526. 
46 



722 INDEX OF DISEASES 

Debility : 

See Neurasthenia. 

Delirium of Low Fevers : 

blisters, when condition is not due to exhaustion, 603. 
chloral, in early stages, 79. 
valerian, 16. 

Delirium Tremens: 

chloral, to produce sleep, powerful but depressant, 79. 
chloretone, a very uncertain hypnotic, 92. 
digitalis, to maintain circulation, large doses well borne, 230. 
hops, 18. 

hyoscine hydrobromide, a useful hypnotic, especially in combination with mor- 
phine,. 110. 
monobromated camphor, of little value, 161. 
opium, serviceable, but not to be used too lavishly, 64. 
paraldehyde, a useful somnifacient, 88. 

potassium bromide, as a general nerve sedative, not to produce sleep, 157. 
valerian, too feeble, 16. 

Dermatitis : 

vinegar, a soothing astringent lotion, 290. 

Diabetes Insipidus : 

antipyrine, 464. 

ergot, probably the most generally useful remedy known, 589. 

opium, may be used in combination with gallic acid, 65. 

Diabetes Mellitus: 

antipyrine, 464. 

arsenical solution of lithium, in gouty cases, (note) 543. 

ergot, may do good, usually fails, 589. 

eucalyptus, 442. 

glycerin, as a sweetening agent instead of sugar, 626. 

hydrogen dioxide, probably of no service, 662. 

jambul, in some cases may greatly reduce sugar, usually no effect, 398. 

lecithin, recommended to improve nutrition, 399. 

opium, the most valuable drug in this condition, use in large doses, 65. 

piperazine, recommended on scientific grounds, (note) 544. 

saccharin, extraordinarily sweet, used as substitute for sugar, 627. 

salicylic acid, has been highly commended, 452. 

sodium carbonate, 634. 

Diarrhoea : 

antacids, in cases with "spinach-stools," 631. 

antipyrin, 464. 

argentol, as an astringent antiseptic, 319. 

aromatics, in diarrhoeas of relaxation, 479 

astringents, 284. 

atropine, in colliquative diarrhoeas, 105. 

bismuth and ammonium citrate, differs essentially from other salts of bismuth, 

useful only in serous types, 307. 
bismuth, the insoluble salts of bismuth are the most generally valuable remedies 

we have in diarrhoeas of an inflammatory character, their action is sedative, 

protective antiseptic and astringent, 306. 
calcium, carbonate, in summer diarrhoeas when intestines are acid, 637. 
camphor, in serous forms of diarrhoea, 191. 

castor oil, useful to cleanse bowel in inflammatory diarrhoea, is sedative, 521. 
cocaine, 126. 

copaiba, in chronic cases, 553. 

copper sulphate, used in chronic ulcerative types, but is of little value, 310. 
creosote, intestinal antiseptic 675. 
cresol, antiseptic, 679. 
ergot, in chronic serous diarrhoeas restores tone to relaxed vessels, a valuable 

remedy, 588. 



INDEX OF DISEASES 723 

Diarrhoea (Continual): 

hamatoxylon, efficient astringenl with pleasant taste 288 

Hopes camphor mixture, a valuable combination in serous diarrhoeas 882 

ipecacuanha, in chronic cases, 491 

jambul, 398 

bad acetate, employed in serous diarrhoeas combined with opium 294 

magnesia, in cases with intestinal acidity, 835. 

naphtol, a valuable intestinal antiseptic, 681. 

nuro-hydnxhloric acid, in chronic cases with hepatic torpor :»:;:!. 

nitrous acid, preferred in Hope's camphor mixture to nitric acid :i:i' > 

opium, lessens both peristalsis and secretions, to be Used in serous, not in mucous 

diarrhoeas, 65. 
phenol, a.s an intestinal antiseptic, 6(59. 

rhubarb, cathartic and astringent; of service in summer complaint 504 
sodium phosphate, useful in chronic diarrhoea of infants, 511. 
strychnine, in atonic cases, 139. 
sulphuric add, an active astringent, 330. 
syrup of lime, <>:>7. 
tanna/bin, possesses the astringent properties of tannin without deleterious effects 

upon the stomach, 289. 
tannic acid, in serous types t,> check excessive secretion, 286. 
tannoform, claimed to combine antiseptic influence of formaldehyde to astrin- 

gency of tannin, 290. 
tannopine, 2S9. 

sine oxide, in chronic catarrhal varieties, 308. 
tine sulphate, in chronic diarrhoea with ulcerations, 308. 

Digitalis-poisoning : 

treatment of, 233. 

Dilatation of Heart : 

conrallaria, 247. 

digitalis, 227. 

Diphtheria : 
antitoxin, specific, use early and freely, 408. 
benzoic acid, locally as antiseptic, 692. 
boric acid, 698. 

colloidal silver, used by inunction, of doubtful value, 320. 
creosote, apply locally as antiseptic, 676. 
hydrochloric acid, to destroy membrane, 331. 

hydrogen dioxide, one of the most useful germicides, apply with swab, 662. 
jaborandi, 567. 

lime-water, to dissolve the membrane, 637. 
mercury, after antitoxin probably the most valuable internal remedy; calomel 

may be dusted on diseased surface, 367. 
jxipain, to dissolve membrane, 651. 
phenol, germicidal, may be used in form of lozenge, 669. 
resorcinol, antiseptic and feebly caustic, 685. 
streptococcus antitoxin, may be used for mixed infections, 411 
tincture of ferric chloride, value doubtful, 328. 

Dislocation : 

anaesthetics, 22. 

Dropsy : 

apocynum, diuretic and cardiac stimulant, 237 

blisters, in local dropsies, 603. 

Kiffcinc, actively diuretic, 217. 

calomel, a powerful diuretic if used in large doses, 530. 

cathartics, 499. 

convaUaria, is diuretic and sometimes cathartic, 247. 

diaphoretics, 561. 

digitalis, increases urinary secretion by stimulating the circulation, 229. 

diuretics, 527. 

elaterin, hydragogue cathartic, especially useful in renal dropsies, 519. 



724 INDEX OF DISEASES 

Dropsy (Continued): 
jaborandi, eliminates the fluid through the skin, 567. 

jalap, hydragogue cathartic, use in the form of compound jalap powder, 516. 
magnesium sulphate, eliminates fluid through the bowels, 507. 
potassium nitrate, 539. 

potassium bitartrate, non-irritant diuretic, 539. 
scoparius, diuretic but irritant to kidneys, 530. 
squill, powerful diuretic, avoid in acute Bright's disease, 529. 
strophanthus, cardiac stimulant, lias more action on kidneys than digitalis, 241. 
sugar, 544. 

theobromine, useful in either cardiac or nephritic dropsy, 532. 
theocin, diuretic 532. 

Dysentery : 

calomel, internally in fractional doses every hour, antiphlogistic and purgative, 

515. 
castor oil, purgative, also soothing to inflamed mucous membrane, 522. 
cathartics, 499. 

cocaine, in the form of suppositories when irritability of rectum, 126. 
copaiba, in chronic cases, 553. 
creosote, 676. 
enemata, a very important part of the treatment of dysentery is the application 

of various drugs to the inflamed area by means of the high enema, 501. 
ergot, useful in chronic cases, 588. 
flaxseed, to be used freely in form of decoction, 619. 
glycerin, applied locally by means of enema, 626. 
iodine, 378. 

iodoform, in the form of suppositories as local anodyne, 384. 
ipecacuanha, except the purgatives ipecac in large doses the most valuable drug 

which can be given by mouth, 491. 
naphtol, 681. 

nitrous acid, in chronic dysentery of hot climates, 332. 
opium, acts as antiphlogistic and analgesic, 65. 

potassium chlorate, useful for rectal injections in chronic cases, 541. 
potassium permanganate, wash out colon with one to two thousand solution, 660. 
silver nitrate, by rectal injection in chronic cases, 317. 
sulphur, seems to act as intestinal antiseptic, highly recommended, 694. 

Dysmenorrhea : 

amyl nitrite, in spasmodic type, 168. 

antipyrine, to relieve pain, 463. 

atropine, in spasmodic type, 104. 

camphor, in nervous cases, 191. 

cotton-root, has stimulant action of the uterus, 598. 

hydrastinine hydrochlorate, stimulant to uterus, 597. 

viburnum, 581. 

Dyspepsia : 

alcohol, often relieves, but danger of habit, 205. 

antacids, curative as well as alleviating, 631. 

asafetida, in atonic cases, 17. 

calcium chloride, recommended in fermentative cases, 637. 

charcoal, as an absorbent in fermentative dyspepsia, 652. 

enemata, 500. 

euonymus, as a laxative, 520. 

ginger, must not be used when there is inflammation, 482. 

Hydrastis, 595. 

hydrochloric acid, as a digestant where insufficient gastric secretion, 331. 

magnesia, laxative and antacid, 635. 

naphtol, antiseptic, useful where much fermentation, 681. 

nitric acid, to replace the hydrochloric acid of stomach, 332. 

pancreatin, cannot have any effect as digestant, 649. 

pepper, may be used in atonic types, 483. 

pepsin, used where gastric secretion fails, usually of little benefit, 648. 

physostigma, in intestinal dyspepsia, 151. 



INDEX OF DISEASES 725 

Dyspepsia (Continued) : 

silver nitrate, valuable astringent in true gastritis, especially when uloer present, 

;u7. 
soda, convrts hyperacidity, encourages gastric secretion, 634. 
strychnine, when associated with atony, 139. 
taraxacum, 397. 
terebene, in flatulent intestinal dyspepsia, 575. 

Dyspnoea : 

aspidosperma, active respiratory stimulant, 180. 
mi/camphor, respiratory sedative and cardiac stimulant, 192. 
physosttgma, when dependent on bronchitis, 161. 

Eclampsia : 

See Puerpbral Convulsions. 

Eczema : 

arsenic, internally, beneficial in chronic cases, 351. 

betanaphtol, oily solution, locaily applied, 681. 

eacodylic acid, an arsenical preparation, 359. 

glycerin, useful emollient, 626. 

ichtkargan, 320. 

ichthyol, a very useful external application, 396. 

menthol, to relieve itching, 682. 

papain, to destroy thickened skin, 651. 

resorcinol, a valuable local application in chronic cases, 685. 

soft soap, 600. 

suprarenal capsule, to blanch reddened areas in chronic cases, 245. 

In nnoform, 290. 

zinc oxide ointment, a useful astringent application, 309. 

Effusion, Pericardial : 

potassium iodide, aids the absorption of fluids, 377 
squill, eliminates fluid through kidneys, 529. 

Effusion, Pleural: 

antipyrine, 464. 

iodoform, as a substitute for iodides, 382. 

potassium iodide, 377. 

squill, 529. 

sugar, diuretic, 544. 

Emesis : 

See Vomiting. 

Emphysema : 

aspidosperma, 180. 

Empyema : 

creosote, locally as disinfectant, 676. 

iodine, inject after cleaning out cavity, 378. 

iodoform, in tuberculous cases; glycerin solution locally applied, 384. 

Endocarditis : 

aconite, when cardiac excitement or excessive hypertrophy, 273. 
camphor, as a stimulant where immediate danger of heart failure, 191. 
convallaria, much disagreement as to its value, 247. 

digitalis, the most reliable stimulant and heart tonic in all cases where com- 
pensation is lost, 228. 
mercury, 367. 

sparteine, occasionally of service as heart stimulant, 250. 
suprarenal extract, value very doubtful, 246. 
See also Heart Disease. 



720 INDEX OF DISEASES 

Endometritis : 

hydrastinine hydrochhratc , 597. 
thyroid extract, 496. 

Enteric Fever: 

See Typhoid Fever. 

Enteritis : 

ammonium chloride, 186. 

bismuth, the insoluble salts of bismuth (subnitrate, subcarbonate, subgallate, 
subsalicylate) are our most efficient remedies in enteritis, 306. 

castor oil, useful to cleanse the bowel, also sedative to inflamed mucosa, 521. 

cathartics, benefit by getting rid of irritating substance, use in beginning of treat- 
ment, 499. 

chlorine, recommended as an intestinal antiseptic, 659. 

copper sulpluite, 310. 

demulcents, soothe the inflammation, use in acute cases, 617. 

enemata, 501. 

flaxseed, used as demulcent in the form of a decoction, 619. 

hydrastis, beneficial especially in chronic cases, 595. 

magnesium sulphate, a non-irritating cathartic, 507. 

naphtalin, as an intestinal disinfectant, 680. 

opium, should be used for antiphlogistic effects, not to check the diarrhoea, 65. 

phenyl salicylate, as intestinal antiseptic, 673. 

physostigma, in chronic cases, 151. 

resorcinol, 684. 

silver nitrate, 317. 

slippery elm, demulcent, 618. 

tannalbin, a non-irritant astringent, 289. 

See also Diarrhcea. 

Enuresis : 

See Incontinence op Urine: 

Ephemeral Fever: 

aconite, 273. 

Epididymitis : 

silver nitrate, painted over the scrotum, 317. 

Epilepsy : 

acetanilid, 469. 

amyl nitrite, in cases with a distinct aura, or in status epilepticus, 167. 

anaesthetics, rarely needed except in status epilepticus, 22. 

antipyrine, efficacious in some cases, may be tried in any, 463. 

borax, probably of no value, 698. 

bromipin, administered either hypodermically or by inunction, 160. 

camphor, 191. 

chhretone, recommended especially in petit mal, 92. 

ergot, increases effect of bromides, 589. 

hydrastinine hydrochlorate, theoretically is strongly indicated, 598. 

hydrobromic acid salts, the standard remedies, 157. 

physostigma, of very doubtful value, 151. 

pituitary body, no good, 407. 

santonin, 640. 

silver nitrate, useless, 317. 

sulphonal, 87. 

zinc bromide, by some believed of service, but doubtful if of value, 309. 

zinc oxide, 309. 

Episcleritis : 

physostigmine, 152. 

Epistaxis : 

cocaine, acts by constricting blood-vessels, 126. 

gelatin, may be employed with advantage both locally and internally, 401. 
suprarenal extract, a very powerful local constrictor of blood-vessels, 245. 
tannic acid, acts by coagulating blood and contracting vessels, 2S6. 






INDEX OF DISEASES 727 

Epithelioma : 
resorctnoZ, as a caustic, tkS5. 

Erysipelas : 

antipyrine, to reduce the temperature, 462. 

atropine, as :i circulatory siiuiulant, 105 
benzoic acid, as an antiseptic, ti'.l'_ > . 
boric <«•<'</. saturated solution applied locally, 698 
creosote, used in the form of an ointment, f>7<>. 
ichthyol. 396. 

iodine, beneficial results from local application hut must not be used too freelv 
377. " 

phenol, deep injections, 669. 

streptococcus antitoxin, has not fulfilled expectations, but may be tried, 410. 
tincture of ferric chloride, specific action from internal use, 328. 

Excoriations : 

glycerin, soothing and softening, 626. 

Exophthalmic Goitre : 

picric acid, 647. 

speuieine, to relieve the cardiac symptoms, 250. 
splenic extract, well worth trying, 407. 
strophantus, to control the heart action, 241. 

Fatty Heart: 

See Heart Disease. 

Faucitis : 

See Sore Throat. 

Favus : 

naphthol, in the form of a soap, 681. 

Fecal Accumulation : 

black draught, a very efficient remedy, 507. 
Epsom salt, 507. 
senna, 507. 

Feet, Sweating of : 

See Hyperidrosis. 

Feet, Tender : 

tannic acid, 286 

Felon : 

carbolic acid, injected deeply, 669. 

silver nitrate, to abort, paint finger with solution of, 319. 

Fever : 

acetanilid, probably less depressant than antipyrin, 469. 

acetopyrin, coal tar antipyretic, 466. 

aconite, useful febrifuge in mild fevers, 273. 

alcohol, acts as necessary food and cardiac stimulant, 203. 

ammonia, to combat collapse, 185. 

antipyretics, less serviceable than cold bath in severe fever, 445. 

antipyrine, to lessen fever, 462. 

aspirin, especially in rheumatic fever, 456. 

cardiac depressants, increase heat elimination, 256. 

chloral, as a sedative, 79. 

diaphoretics, useful to break up some kinds of fever, 561. 

digitalis, to maintain circulation, 231. 

diuretics, water especially useful in febrile conditions, 527. 

gelsemium, as arterial sedative in sthenic fevers, 173. 

hydrogen dioxide, probably no value, 662. 



728 INDEX OF DISEASES 

Fever (Continued) : 

jaborandi, efficacious sudorific, 567. 

lemon-juice, as refrigerant drink, 513. 

nitric acid, 332. 

oil of turpentine, 551. 

opium, to support the system, 65. 

phenacetin, probably safest of coal-tar antipyretics, 471. 

phenocoll hydrochloride, AT2. 

salicylic acid, not generally useful as antipyretic, 451 . 

saloquinine, 437. 

See also Typhoid Fever, Scarlet Fever, etc. 

Fibroid Tumors of Uterus : 

See Uterus, Fibroid Tumors of. 

Fissure of Anus : 

atropine, to relieve accompanying spasm, 104. 
benzoic acid, antiseptic and healing, 693. 
cocaine, as a local anesthetic, 126. 
iodoform, a valuable local anaesthetic, 382. 

Fistula : 

creosote, 676. 

Flatulence : 

aromatics, to stimulate intestinal peristalsis, 479. 
asafetida, enemata in flatulent constipation, 17. 
Hoffmann's anodyne, carminative, 29. 
physostigma, a stimulant to intestinal muscle, 151. 
See also Colic. 

Fractures : 

calcium phosphate, in ununited fractures, 336. 

sulphonal, to relieve muscular spasm, 84. 

thyroid extract, lias sometimes proved useful in delayed union, 406. 

Frost- Bites : 

ichihyol, 396. 

Furuncles : 

See Boils. 

Galactorrhea : 

antipyrine, 464. 

belladonna, either internally or applied locally to breasts, 105. 

ergot, 588. 

Gall- Stones : 

See Calculi. 

Gangrene : 

nitric acid, 332. 

Gangrene of the Lungs : 

phenol, 669. 

Gastralgia : 

arsenic, in neuralgic types, 352. 

bismuth, especially in feeble patients, 306. 

hydrocyanic acid, a useful remedy, probably acts on sensory nerves, 280. 

manganese dioxide, 329. 

orthoform, useful in cases of gastric ulcer, 52. 

phenol, of value on account of local anaesthetic action as well as antiseptic, 668. 

Gastric Crisis : 

See Locomotor Ataxia. 



INDEX OF DISEASES 

Gastric Ulcer: 

copaiba, as a stimulant in chronic and indolent ulcers, ">.">:>. 
ichthargan, a combination oi silver and iohthyol. 321. 

ortho/orm, to lessen pain through local anaesthetic effect, 52. 

resorcinol, a not generally useful remedy, 68 I 

S%h)«r nitrate, the standard remedy, sedative, astringent, and antiseptic, 817 

Gastric Uneasiness : 
antacids, 631. 

Gastritis : 

ammonium chloride, in chronic cases, 1S6. 

bismuth, all its insoluble salts act similarly; they are sedative, astringenl pro- 
tective, and antiseptic, 306. 
calcium chloride, 637. 

demulcents, in acute inflammations may be freely employed, 6] , 
hydrastis, useful especially in chronic eases, 595. 
ichthargan, 321. 

silver nitrate, useful sedative astringent, 317. 
See also Dyspepsia. 

Gelsemium Poisoning: 

treatment of, 174. 

Glands, Enlarged: 

cod-liver oil, to improve nutrition in scrofula, 390. 

ichthyol, applied externally, 396. 

iodine, used externally in indolent hypertrophy, 378. 

iodoform, either by mouth (382) or glycerin solution injected into tuberculous 

glands, 384. 
-phenol, deeply injected, 669. 
sulphurated lime, 694. 
thiosinamine, especially in cases with fibrous tissue, 398. 

Glaucoma : 

dionine, used locally increases the flow of lymph in the eye, 74. 
physostigmine, relieves ocular tension by contracting the pupil, 152. 
salicylic acid, useful especially in rheumatic cases, 452. 

Gleet : 

cantharides, a powerful stimulant to the urethral mucous membrane, 600. 
tincture of ferric chloride, in combination with cantharides, 328. 
turpentine, a stimulant alterative diuretic, 551. 

Glycosuria : 

See Diabetes Mellitus. 

Goitre : 

fluorides, 659. 

iodine, useful in true goitre, 376. 

thyroid extract, only in simple goitre, not in exophthalmic, 406. 

Goitre, Exophthalmic : 

See Exophthalmic Goitre. 

Gonorrhoea : 

acetozone, locally as antiseptic, 663. 

albargin, a silver preparation, 319. 

antimony, internally as a circulatory depressant and diaphoretic, 260. 

argonin, a silver preparation, 320. 

benzoic acid, internally as urinary antiseptic, 693 

betol, given internally, 681. 

bismuth, used locally in early stages, 306. 

copaiba, in the beginning stages employed internally, 553. 

hydrastin, locally in the later stages, 595. 

hydrogen dioxide, 662. 



730 INDEX OF DISEASES 

Gonorrhoea (Continued) : 

ichttiargan, active silver preparation, 320. 

kava, 556. 

largin, recommended especially in gonorrhoea in women, 319. 

matico, 554. 

methylene-blue, of doubtful value, 439. 

oil of erigeron, 555. 

oil of sandal-wood, used internally in the advanced stages, 555. 

pareira, in chronic gonorrhoea as alterative diuretic, 547. 

potassium bromide, to allay sexual excitement, 158. 

protargol, an organic silver preparation, 321. 

quinine, applied locally, 432. 

resorcinol, 684. 

silver citrate, claimed to be non-irritant and actively germicidal, 319. 

silver nitrate, especially useful in chronic cases, 316. 

silver sulphocarbolate, 319. 

terpin hydrate, used internally, 575. 

zinc acetate, 309. 

Gout: 

cathartics, 500. 

colchicum, most useful in typical gout (podagra), 393. 

ichthyol, as an external application, 396. 

lithium, supposed to be depurant and to increase solubility of urates, 543. 

magnesia, antacid and laxative, 635. 

piperazine, occasionally useful in chronic cases, 543. 

potassium iodide, of some service in irregular or chronic gout, 376. 

salicylates, used in combination with colchicum, 451. 

sulphur, 694. 

sulphuretted hydrogen, in chronic cases, 578. 

water, 526. 

Granular Conjunctivitis : 

See Conjunctivitis. 

Granulations, Exuberant : 

burnt alum, caustic and astringent, 616. 

copper sulphate, antiseptic astringent and mildly caustic, 616. 

silver nitrate, caustic and powerfully germicidal, 316. 

zinc sulphate, 616. 

Gravel : 

benzoic acid, probably lessens uric acid excretion, 863. 

potassium salts, renders urine alkaline, also lessens formation of uric acid, 538. 

soda, less valuable than potash salts, 634. 

Graves's Disease : 

See Exophthalmic Goitre. 

Grippe : 

See Influenza. 

Gummata : 

See Syphilis. 

Gums, Retraction of: 

iodine, applied locally by means of camel's-hair brush, 378. 

Hay Fever: 

antitoxin, 411. 

atropine, to check excessive nasal secretion, 105. 
cocaine, applied locally, relieves congestion and is anaesthetic, 126. 
quinine, locally applied, probably not of much value, 432. 
resorcinol, 684. 

suprarenal extract, probably the most useful remedy known for local application, 
245. 






INDEX OF DISEASES 731 

Headache : 

ammonia, when due to sick stomach, S32, 

ammonium valerate, 10. 

antacids, in gastric headaches to oorreol hyperacidity, 032. 

(intipi/riiu-, promptly acting coal-tar analgesic, 163. ' 

caffeine, especially useful in conjunction with coal tars, 210. 

camphor, in nervous types, 191. 

emetics, 487. 

ergot, in congestive headaches, 589. 

ether, in hysterical or nervous cases, 30. 

magnesia, antacid laxative in eases with gastric disturbances, 635. 

phemieetin, one of the most valuable of the coal tars, 171. 

strychnine, when associated with optic atrophy, 138. 
See also Migraine and Neuralgia. 

Heartburn : 

See Cardialgi.y. 

Heart Disease : 

adonulin, a heart stimulant, 252. 

apocynum, acts on the heart like digitalis but is more diuretic, 237. 

caffeine, useful as a temporary stimulant, 217. 

convallaria, employed especially when dropsy, 217 

digitalis, the most usefid drug known in all forms of prolonged heart failure 

is both stimulant and tonic to heart muscle, 227. 
mercury, as an antiphlogistic in acute endocarditis, 367. 
sparteine, 250. 

stropharithus, very similar to digitalis, but more prompt and less powerful, 241. 
strychnine, especially valuable where muscular weakness or degeneration, 139. 
suprarenal extract, of doubt fid utility, 246. 
See- also Endocarditis, Angina Pectoris. 

Heart Failure: 

alcohol, promptly acting, not very powerful, 204. 

ammonia, must be given hypodermically to have an effect, 185. 

amyl nitrite, 168. 

caffeine, useful in cases not too acute, 217. 

camphor, hypodermically in olive oil, a very powerful resuscitant, 191. 

digitalis, 230. 

strophanthus , 241. 

suprarenal extract, a dangerous drug, 245. 

Heart, Palpitation of : 

convallaria, 247. 
sparteine, 250. 

Hematemesis : 

gelatin, increases the coagulability of blood, especially useful in subacute cases, 401. 

Monsel's solution, one of the most trustworthy styptics in acute cases, 327. 

suprarenal extract acts by constricting vessels at bleeding point, 245. 

tannic acid, 286. 

vinegar, useful especially in emergencies — is quite efficient, 290. 

Hematuria : 

gallic acid, perhaps the most generally useful remedy, 287. 

gelatin, believed by some to be irritant to kidneys, is probably beneficial, 401. 

turpentine, in passive hemorrhage, 551. 

See also Black-water Fever. 

Hemophilia : 

gelatin, 401. 

Hemoptysis : 

alum, used by atomization, 292. 

atomization, as a means of applying remedies locally to lungs, 572. 

cotarnine, 291. 



732 INDEX OF DISEASES 

Hemoptysis (Continued): 

ergot, commonly used, but doubtful if of service, 588. 
gallic acid, given internally, 287. 

gelatin, probably most useful drug known (except opiates); increases coag- 
ulability of blood, 401. 
ipecacuanha, claimed to be specific, 492. 
lead acetate, doubtful if of service, 294. 
M ousel's solution, applied by atomization, 327. 
oil of turpentine, 551. 
opium, some form of opium or morphine should always be given, 64. 

Hemicrania : 
See Migraine. 

Hemiplegia : 

strychnine, avoid during early stages, later useful as general tonic, 138. 

Hemorrhage from the Bowels : 

oil of turpentine, 551. 

suprarenal extract, acts locally by constricting vessels, 245. 

tannic acid, best given in form of crude galenical rather than pure tannin, 286. 

Hemorrhages : 

alum, precipitates albumin of blood, forming hard coagulum, 292 

astringents, 284. 

cocaine, applied locally powerfully constricts vessels, 126. 

cotarninc, highly praised in both internal and local bleeding, 291. 

creosote, useful only to check capillary oozing, 675. 

ergot, widely used but probably no good, 588. 

gelatin, hastens the clotting of blood, useful either locally or internally, 401. 

ipecacuanha, 492. 

lead acetate, 294. 

matico, in external hemorrhages, acts mechanically, 554. 

Monsel's solution, a powerful styptic and astringent when locally applied, 327. 

oil of erigeron, 555. 

oil of turpentine, 551. 

sulphuric acid, 331. 

suprarenal extract, locally applied, a very useful drug, contracts blood-vessels, 

245. _ 
tannic acid, for local application, 288. 

Hemorrhoids : 

aloes, as a laxative, 506. 
belladonna, as a local anodyne, 106. 

cocaine, local anaesthetic and constrictor of blood-vessels, 126. 
cubebs, used internally in chronic types, 554. 
enemata, 500. 

glycerin, used as laxative, 626. 
infiltration anaesthesia, for operative purposes, 54. 
iodoform, in suppositories a very useful anodyne, 382. 

potassium chlorate, saturated solution injected into the rectum a useful treat- 
ment, 541. 
sulphur, as a laxative, 694. 

tannic acid, useful astringent in form of ointment, 286. 
tobacco, 175. 

Hepatic Congestion and Torpor: 

ammonium chlorule, a useful remedy in chronic cases, 186. 

calomel, probably most generally serviceable remedy in acute cases, 515. 

cathartics, 499. 

chlorine, 659. 

emetics, 487. 

euonymus, used in chronic cases, 520. 

ipecacuanha, frequently of service, 491. 

lemon-juice, employed in habitual hepatic torpor, 513. 

nitric acid, 332. 



INIH'A OF DISEASES 783 

Hepatic Congestion and Torpor (Continued)'. 

nitro-hydrochloric acid, one of the best remedies in chronic cases, :>:>.'>. 
potassium sails, act as depurants by increasing oxidation, 688. 
soda, in chronic cases, 634. 
sodium phosphate, of value in chronic cases with constipation, 611. 

Hepatitis : 

ammonium chloride, in chronic cases, 186. 
mercury, as antiphlogistic rather than purgative, ->t >T . 

nitro-hydrochloric arid, in chronic cases, may be used internally or in form of 
bath, 333. 

Herpes : 

naphtol, in the form of a soap, 681. 
salicylic acid, useful in corneal herpes, 452. 

Hiccough : 

atropine, 104. 

chloral, acts by depression of motor centres, 80. 

ether, acts locally on stomach, also on nervous centres, 30. 

musk, claimed to be almost a specific, 15. 

sulphonal, antispasmodic effect, 84. 

Hospital Gangrene : 

bromine, a very active caustic and germicidal agent, 616. 
nitric acid, actively caustic, 332. 

Hydrocele : 

iodine, inject directly into sac, 378. 
phenol, deep injections of, 669. 

Hydrocephalus : 

potassium iodide, 377. 

Hydrophobia : 

caustic potash, applied to bite as a prophylactic, 612. 
cscharoties, 611. 

Hyperacidity : 

See Acidity of Stomach. 

Hyperemesis : 

See Vomiting. 

Hyperidrosis : 

arsenic, internally in neurotic cases, 351. 

chalk, applied locally as a desiccant, 637. 

tannic acid, used in form of wash, 286. 

tannojorm, astringent and antiseptic dusting powder, 290. 

See also Night-Sweats. 

Hyperpyrexia : 

See Fever. 
Hypertrophy of Heart: 

aconite, 273. 
Hypochondriasis : 

alcohol, 205. 
cypripedium, 19. 



Hysteria : 

anesthetics, to check convulsions, 21. 
antipyrine, in convulsive cases, 462. 
asafetida, a useful nerve sedative, 17. 



734 INDEX OF DISEASES 

Hysteria (Continued): 

bromides, probably the most widely used remedies, 157. 

camphor, useful as a nerve sedative and anticonvulsant, 191. 

cocaine, as a stimulant and stomachic, 126. 

conium, 178. 

creosote, to check hysterical vomiting, 675. 

ether, given internally, 30. 

gold and sodium chloride, 373. 

monobromated camphor, 161. 

musk, 15. 

oil of wormseed, 643. 

sparteine, 250. 

sumbul, especially in cases with uterine disturbances, 17. 

valerian, a mildly acting but widely useful drug, 16. 

Ichthyosis : 

naphtol, 681 

Idiocy : 

thyroid extract, valuable probably only in myxedematous subjects, 406. 

Ileus : 

See Intestinal Obstruction. 

Impotence : 

turpentine, 551. 

yohimbine, useful only in neurasthenic cases, not in organic, 556 

Incontinence of Urine: 

antipyrine, in spasmodic cases, 463. 

atropine, when due to irritability of bladder, 104. 

chloral, in spasmodic cases, 80. 

quinine, in large doses frequently useful, 430. 

strychnine, when due to nervous relaxation, 139. 

turpentine, in atonic forms, 551. 

Indigestion : 

See Dyspepsia. 

Infantile Colic: 

See Colic. 

Infantile Convulsions : 

See Convulsions. 

Infantile Diarrhoea: 

See Cholera Infantum. 

Inflammations : 

belladonna, locally applied as anodyne, 105. 

blisters, useful in serous and other internal inflammations, 603. 

carbolic acid, deep injections, in deep-seated inflammations of chronic type, 669. 

lead acetate, sedative astringent embrocation, especially in acute conditions, 294. 

mercury, especially valuable in serous inflammations, may be used internally or 

externally, 367. 
opium, seems to exercise a specific antiphlogistic effect, 65. 
silver nitrate, applied locally to inflamed mucous membranes, 317. 
solution of lead subacetate, 294. 
tartar emetic, to quiet arterial excitement in sthenic inflammations, 260 

Influenza : 

aconite, to encourage sweating, 273. 

betanaphtol, 681. 

pilocarpine, used to produce sweat will sometimes abort, 567. 



INDEX OF DISEASES 73S 

Insanity : 
ehioretone, used as a somnifacient, uncertain, 92. 

hyoscinc hydrobrom idv , acts as hypnotic and in some cases seems to have curative 

effect, 111). 
paraldehyde, one of the most valuable somnifacients, 88. 
spla-n extract, 107. 
vernol, as a hypnotic, 91. 
See also Mania. 

Insomnia : 

See Sleeplessness. 

Intermittent Fever : 
See Malaria. 

Intertrigo : 

chalk, protective and desiccant, 637. 
ichthyol, 396. 

Intestinal Atony : 

physostigma , the most useful stimulant to unstriped muscle fibre known, LSI. 

Intestinal Catarrh : 

See Enteritis. 

Intestinal Indigestion : 

betanaphtol, to check fermentation, 681. 
physostigma, 151. 
salol, antiseptic, 673. 

Intestinal Obstruction : 

atropine, when due to intestinal spasm, 104. 
opium, in spasmodic or irritative types, 6.5. 

Iritis and Iridocyclitis : 

atropine, to rest eye and prevent adhesions, best mydriatic for this purpose, 106. 

dionine, increases the flow of lymph in eye, 74. 

mercury, in cases with marked lymphatic exudation, 367. 

salicylic acid, especially but not exclusively useful in rheumatic persons, 452. 

santonin, in amaurosis following iritis, 640. 

thiosinamine, probably of very little value, 398. 

Irritable Bladder: 

See Bladder, Irritable. 

Irritable Heart : 

digitalis, 229. 

Itch: 

See Scabies. 

Ivy=Poisoning: 

See Rhus-Toxicodendron Poisoning. 

Jaundice : 

ammonium chloride, in chronic torpor of the liver and catarrhal jaundice, L86. 

emetics, to relieve portal congestion, 487. 

forced enemata, 501. 

ipecacuanha, 491. 

lemon-juice, in catarrhal jaundice, 513. 

mercury, probably the most generally serviceable drug in catarrhal jaundice 

and acute biliousness, 515. 
nitro-hydrochloric acid, especially valuable in cases depending on chronic hepatic 

torpor, 333. 
oxgall, most powerful stimulant to hepatic secretion known, 50S. 



736 INDEX OF DISEASES 

Jaundice (Continued): 

potassium salts, depurant and alkaline; useful in chronic hepatic torpor and 

catarrhal jaundice, 538. 
sodium phosphate, in chronic cases with constipation, 511. 
sodium salts, alkalies of value, 634. 

Joints, Inflammation of: 

blisters, in chronic cases, 603. 

cautery, 604. 

cod-liver oil, in tuberculous joint diseases, 390. 

gold and sodium chloride, 377. 

ichthyol, especially in gouty or rheumatic forms, 

iodine, internally as alterative (376) or externally as a counter-irritant, 378. 

iodoform, injected into the joint directly, in tuberculous arthritis, 384. 

Keloid : 

ichthyol, locally applied, 396. 

thiosinamine, may be used either internally or injected locally, 398. 

thyroid extract, recommended highly for internal use, 403. 

Keratitis : 

atropine, to lessen liability to iritis, 106. 

dionine, increases lymph flow in eye, 74. 

iodipin, 380. 

physostigmine, to reduce vascularization, 152. 

salicylic acid, especially, but not exclusively, useful in rheumatic cases, 452. 

Labor : 

anaesthetics, to allay the suffering, 22. 

chloral, to iessen pain and overcome rigidity of os, 80. 

ergot, to increase uterine contractions, used only in later stages, 586. 

Laryngismus stridulus : 

antipyrine, 463. 
atropine, 104. 
chloral, 80. 
expectorants, 571. 

Laryngitis : 

camphor-menthol, dissolved in liquid petrolatum and used as spray, (note) 682. 

cocaine, applied locally as palliative, 126. 

gelsemium, internally in spasmodic types, 173. 

glycerin, locally applied has a demulcent effect, 626. 

heroine, used as local anaesthetic in laryngeal tuberculosis, 75. 

ichthargan, a solution in glycerin as a spray, 320. 

lactic acid, as a caustic in tuberculous laryngitis, 616. 

mercury, administered internally as antiphlogistic, 367. 

menthol, dissolved in liquid petrolatum and applied by atomization, 682. 

naphtol, 681. 

orthoform, a valuable local anaesthetic in tuberculous laryngitis, 52. 

pilocarpine, 567. 

silver nitrate, two per cent, solution applied locally, 316. 

steam atomizer, a very useful method of applying drugs locally, 572. 

suprarenal capsule, 245. 

Lead Poisoning : 

alum, recommended in colica pictonum, 292. 

atropine, most valuable remedy for lead colic known, 104. 

potassium iodide, to increase elimination of lead in chronic poisoning, 377. 

strychnine, of value in plumbic poliomyelitis, 138. 

sulphuric acid, chemical antidote, 331. 

treatment of acute, 295. 

treatment of chronic, 301. 



INDEX OF DISEASES 737 

Lepra: 
iehthyol, 396. 
thioatnamine, 398, 

Leucorrhcea : 

bismuth aubnitrate, sedative astringent, 306, 

creosote, disinfectant, t>7(>. 

iodine, tincture of, locally applied, 378. 

potassium permanganate, disinfectant and deodorant, 860. 

resorcinol, 684. 

tannic acid, astringent, 286. 

Leukaemia : 

eacodylic acid, of no more value than official tonus of arsenic, 359. 
ergot, injected hypodermically, 589. 

Lichen : 

arsenic, 351. 

Lipoma : 

iehthyol, 396 

Lithiemia : 

See Uric Acid Diathesis. 

Liver Diseases : 

See Hepatic. 

Lobelia Poisoning : 

treatment of, 172. 

Locomotor Ataxia : 

acetanilul, for relief of pain, 469. 

antipyrine, for painful crises, 463. 

aspirin, as analgesic, 456. 

glycerophosphates, as nerve tonic, 337. 

hyoscine, as analgesic, 111. 

silver nitrate, used to affect conditions in cord, but of doubtful service, 317. 

Lumbago : 

iehthyol, applied locally, 396. 
potassium iodide, in subacute types, 376. 
."alkylates, the standard remedy, 451. 
sulphur, 694. 

Lumbrici : 
See Round-Worms 

Lupus : 

aristol, as a dusting powder, 387. 

arsenic, as a caustic, 613. 

cantharidin, (note) 605. 

guaiacol, actively germicidal, 676. 

iehthyol, 396. 

phosphorus, internally as a tonic alterative, 340. 

pyrogallol, an ointment used as a caustic, 616. 

thiosinamine, 398. 

thyroid extract, 406. 

Lymphadenitis : 

iehthyol, applied externally in form of ointment, 396. 
sulphurated lime, used internally, 694. 
See also Scrofulosis. 

Lymphoma : 

arsenic, 351. 
47 



738 INDEX OF* DISEASES 

Malaria: 

ammonia, as a heart stimulant in malarial collapse, 185. 

atnyl nitrite, will abruptly end a chill; perhaps useful in pernicious type, 168. 

aristochin, an almost tasteless ester of quinine, 436. 

arsenic, useful especially in chronic or irregular malarias; also in convalescence 

from acute ague, 350. 
chloroform, may be used to abort a chill, 34. 
cinchonine, similar to but less powerful than quinine, 435. 
counter-irritants, in the collapse of pernicious malaria, 603. 
diaphoretics, to shorten duration of paroxysm, 561. 
eucalyptus, frequently of service when quinine contraindicated, 442. 
euquinine, a tasteless substitute for quinine, 436. 
gelsemium, 173. 
methylene-blue, a very powerful antiperiodic, especially valuable where hsematuria, 

438. 
piperine, 483. 

quinine, the standard remedy, best given immediately before paroxysm, 430. 
saloquinine, 437. 
Warburg's tincture, probably the most effectual combination known against the 

more severe types of the disease, 436. 

Malarial Neuralgia: 

arsenic, as an adjunct to cinchona alkaloids, 350. 
quinine, large doses required to produce an effect, 431. 

Malignant Pustule : 

escharotics, 611. 

Mania: 

atropine, when disease dependent on exhaustion, as puerperal mania, 105. 
cathartics, as revulsants, 500. 
chloral, for its somnifacient effect, 79. 
conium, to lessen the motor excitement, 178. 
croton oil, as a revulsant, 522. 

hyoscine hydrobr ornate, seems to have some curative effect as well as general 
sedative action, 110. 

Mania a Potu : 

See Delirium Tremens. 

Mastitis : 

belladonna plaster, 106. 

Masturbation : 

heroine, claimed to be a sexual sedative, 75. 

bromides, the most generally serviceable sexual sedatives known, 158. 

Melancholia : 

alcohol, will often relieve symptoms, but great danger of habit, 205. 

cocaine, of very little service, 126. 

thyroid extract, may be tried, but not likely to be successful, 406. 

Membranous Croup : 

See Croup. 

Meniere's Disease : 

pelletierine, 646. 

Meningitis : 

cautery, the most active form of counter-irritation, 604. 

Menorrhagia : 

aloes, when constipation; acts as laxative and tends to pelvic hyperemia, 506. 

calcium phosphate, when associated with anaemia, 336. 

cotarnine, 291. 

creosote, applied locally, 670. 






INDEX OF DISEASES 789 

Menorrhagia (Continued): 
digitalis, claimed to act as a stimulant to uterine muscles. 281 
•mot, perhaps the most generally efficient remedy known 688 
gelatin, increases coagulability of Mood, may beWd both internally and lonillv 
40 1 . ■> j> 

Hydrastis, 595. 

hydrastinine hydrochlorate, probably acts by causing contraction of womb 597 
oU of erigeron, 555. ' 

sarinc, useful only in conditions of relaxation, 579. 

suprarenal extract, given internally, probably causes uterine contraction 246 
thyroid extract, 40(5. 
viburnum, 581. 

Menstruation, Suppression of: 

See Amenorrhea. 

Mercurial Ptyalism : 

See Ptyalism. 

Metritis : 

bismuth oxyiodogaUatc, employed in form of suppositories, 307. 
creosote, as a disinfectant, especially in puerperal cases, 676. 
ergot, in chronic cases, 588. 

Metrorrhagia : 

ergot, acts by stimulating uterine muscle, 588. 
gelatin, increases coagulation of blood, 401. 
hydrastinine hydrochlorate, 597. 

Migraine : 

acetopyrin, coal-tar analgesic, 466. 

amyl nitrite, in cases with spasm of capillary blood-vessels, 169. 

antipyrine, during paroxysm, to relieve headache, 463. 

aspirin, 456. 

caffeine, sometimes promptly relieves headache, at others fails, 216 

cannabis indica, used as curative between paroxysms 117 

cocaine, 126. 

pyramidon, 472. 

Mitral Disease : 

See Heart Disease. 
Morphine=Poisoning : 

See Opium- Poisoning. 

Morphcea : 

arsenic, 351. 

Multiple Sclerosis : 

acetanilid, 469. 

Muscarine Poisoning : 

atropine, counteracts effects of poison on inhibitory and secretory nerves, 105. 

Muscular Rheumatism : 

See Rheumatism. 

Mush=Room Poisoning : 

See Muscarine Poisoning. 

Myelitis : 

phosphorus, as a reconstructive tonic for nerve centres, 340. 
silver nitrate, value questionable, 317. 

Myocarditis : 

See Heart Disease. 



740 INDEX OF DISEASES 

Myopathy : 

thyroid extract, 406. 






Myxoedema : 

thyroid extract, is a specific, 405. 

Narcotic Poisoning : 

See Poisoning. 

Nasal Catarrh : 

See Rhinitis. 

Nausea : 

See Sick Stomach. 

Nephritis : 

See Bright* Disease. 

Nervous Exhaustion : 

See Neurasthenia. 

Nervous Vomiting : 

See Vomiting. 

Nervousness : 

asafetida, in cases of hysterical type, 17. 

camphor, a very useful sedative, 190. 

bromides, the most reliable sedatives except in hysterical cases, 157. 

valerian, useful in milder forms of hysteria, 16. 

Neuralgia : 

aconite, applied locally, 273. 

alcohol, grave danger of formation of habit, 205. 

antipyrine, one of the best analgesics, 463. 

arsenic, especially but not exclusively useful in malarial cases, 351. 

aspirin, of service in nervous as well as rheumatic types, 456. 

blisters, 604. 

caffeine, very markedly increases the analgesic power of other antineuralgics, 

especially the coal-tar products, 216. 
cannabis indica, used both as an anodyne and as a curative, 1 17. 
carbon disulphide, employed locally as a counter-irritant, 610. 
chloroform, in the form of a liniment, 34. 
cod-liver oil, 390. 

ether, internally sometimes of service, 30. 

gelsemium, used especially as a curative agent in recurring neuralgias, 174. 
hydrocyanic acid, in neuralgia of the stomach, 280. 
iodoform, when syphilitic origin, 382. 

methylene-blue, not so useful as other aniline derivatives, 438. 
pliosphorus, when due to nervous exhaustion, 340. 
potassium bromide, very frequently of service, especially in combination with 

caffeine, 157. 
potassium iodide, in rheumatic or syphilitic cases, 376. 
pyramidon, 472. 

quinine, especially in periodic types, even if not malarial, 431. 
saloquinine, 437. 

veratrine, used externally in form of ointment, but is a dangerous remedy, 266. 
See also Headache. 

Neuralgia, Intermittent : 

See Malarial Neuralgia. 

Neuralgia, Rheumatic : 

See Rheumatic Neuralgia. 



INDEX OF DISEASES , u 

Neurasthenia : 

bromipin, a preparation of bromine, L60. 

coiainf, asa nerve stimulanl and ionic, 126. 

digitalis, when circulation is feeble, 230. 

euquinine, as general tonic, 136. 

glycerophosphates, supposed to represenl phosphorus in easily assimilable form 

luit oi unproved value, 337. 
gold ami sodium (Monde, used as nerve alterative, value doubtful, 373. 
hop*, mildly sedative, useful in nervous unrest, is. 
hypbvhosph ties, 336. 
paraldehyde, as a hypnotic, 88. 
phosphorus, increases reconstructive metabolism of nerve centres, frequently 

of great service, 339. 
sparteine, to relieve cardiac palpitation, 250. 
strychnine, especially useful in chronic eases, i:;s. 
Warburg's tincture, in acute nervous exhaustion, 436 

Neuritis : 

ucetopyrin, to lessen pain, 466. 

aconite, rarely of value, may be used locally, 273. 

atropine, in cases with local muscular spasm, 104. 

blisters, the most generally useful form of counter-irritation, repeat frequently 

as necessary, 603. 
cautery, often valuable in chronic cases, 604 
methylene-blue , to relieve pain, 438. 
salicylates, in rheumatic cases, 451. 
saloquinine, combination of quinic and salicylic acids, 437. 

Night=Pains, Syphilitic : 

iodoform, 3S2. 

Night=Sweats : 

agaric, a very frequently useful remedy, 291. 

alum, to be employed externally, 292. 

atropine, the most generally serviceable remedy known, 105. 

camphoric acid, 192. 

dionine, especially useful in phthisis, as it is also cough sedative, 73. 

ergot, in cases with passive relaxation of blood-vessels, 588. 

gallic acid, 287. 

suiphonal, 84. 

sulphuric acid, one of the best remedies, 330. 

Nipples, Sore : 

benzoic acid, best applied in form of compound tincture of benzoin, antiseptic 

and protective, 693. 
tannic acid, for purpose of hardening, 286. 

Nocturnal Emissions : 

See Spermatorrhoea. 

Nocturnal Enuresis : 

See Incontinence of Urine. 

Nymphomania : 

bromides, in conjunction with hyoscine most efficacious remedy, 158. 

heroine, recommended as sexual sedative, 75. 

hyoscine hydrobromate, has especial action on sexual centres, 111. 

Obesity : 

saccharin, as a sweetening agent free from objections to sugar, 627. 
thyroid extract, will reduce weight temporarily more certainly than any other 
drug, 405. 

Obstruction of Bowels : 

See Intestinal Obstruction. 



742 INDEX OF DISEASES 

Onychia Maligna : 

corrosive sublimate, powerfully germicidal, mildly caustic, 614. 
lead nitrate, to be powdered on inflamed area, 294. 

Ophthalmia : 

iodine, used in scrofulous cases, 378. 

salicylic acid, in sympathetic ophthalmia, 452. 

silver acetate, in ophthalmia neonatorum, 319. 

Opium = liabit : 

cocaine, 126. 
treatment of, 71. 

Opium = Poisoning : 

atropine, as respiratory stimulant, 105. 
caffeine, respiratory and cerebral excitant, 216. 
potassium permanganate, as chemical antidote, 660. 
treatment of, 68. 

Osmidrosis : 

tannic acid, 286. 

Osteomalacia : 

calcium phosphate, 335. 
phosphorus, 340. 

Osteoporosis : 

phosphorus, 340. 

Otitis : 

betanaphtol, as an antiseptic, 681. 
resorcinol, in chronic cases, 684. 

Otorrhcea : 

creosote, as a disinfectant in fetid types, 676. 
hydrastis, acts directly on mucous membrane, 595. 
potassium permanganate, oxidizing disinfectant, 660. 

Ovarian Irritation : 

viburnum, 581. 

Oxalic Acid Diathesis : 

nitric acid, 332. 

nitro-hydrochloric acid, a specific in neurasthenic oxaluria, 333. 

Oxalic=Acid Poisoning: 

treatment of, 686. 

Oxyuris Vermicularis : 

See Seat-Worms. 

Ozaena : 

iodine, an alterative stimulant, 378. 
potassium permanganate, disinfectant, 660. 

Pain: 

acetanilid, when pain of nervous origin, 469. 

aconite, locally applied in neuralgia and similar conditions, 273. 

anaesthetics, of service in severe medical as well as surgical conditions, 21. 

antipyrine, in various nervous pains whether fimctional or organic, 463. 

atropine, as local anodyne, 106. 

cannabis indica, frequently of service although not very powerful, 117. 

chloral, of little use as analgesic, 80. 

chloroform, externally as counter-irritant, 34. 

iodoform, as a local anaesthetic, 382. 



INDEX OF DISEASES 748 

Pain (Continual): 

methylenc-bluc, similar to, generally less useful than other aniline derivative* 438 

opium, the most generally efficient drug, but danger of habit, 64. 

phenacetin, useful in nervous pains, especially in combination with caffeine, 471. 

Palpitation of Heart: 

See Heakt, Palpitation of. 

Papilloma : 

resorcinol, 685. 

Paralysis : 

strychnine, useful only when depressant poison is cause, 138. 

Paralysis Agitans: 

conium, 178. 

hyoscine, a useful palliative, 111. 

Paraplegia, Myelitic : 

phosphorus, may be of service, 340. 
silver nitrate, probably of no value, 317. 

Parturition : 

See Labor. 

Pemphigus : 

arsenic, 351. 

Pericardial Effusions : 

See Effusion, Pericardial. 

Pericarditis : 

mercury, when exudate is fibrinous, 367. 
potassium iodide, in cases with serous effusion, 377. 

Peritonitis : 

blisters, 603. 

iodoform, in tuberculous peritonitis, 384. 

mercury, in sthenic forms of puerperal peritonitis or where fibrinous exudate 

367. 
opium, very useful for its antiphlogistic action as well as checking intestinal 

peristalsis, 65. 
poultices, a useful means of applying heat, 629. 
veratrum, has been highly praised, its tendency to vomit must be controlled by 

opium, 265. 

Pernicious Anaemia: 

iron, of very little service, 326. 

Pernicious Fever : 

See Malarla.. 

Pertussis : 

See Whooping-Cotjgh. 

Petit Mai : 

amyl nitrite, as a diagnostic agent, 168. 

bromides, less generally of service than in major epilepsy, 157. 

chloretone, 92. 

Phagedena : 

nitric acid, as a caustic, 615. 

Phantom Tumor: 

Calabar bean, acts by stimulating intestinal muscles, 151. 



744 INDEX OF DISEASES 

Pharyngitis : 

suprarenal extract, to overcome congestion, 245. 

Phenol-Poisoning : 

treatment of, 672. 

Phlegmons : 

ichthargan, applied in form of ointment, 320. 
phenol, deep injections of value, 669. 

Phosphatic Gravel : 

benzoic acid, 693. 

Phosphaturia : 

benzoic acid, to prevent precipitation of phosphates from urinary fermentation, 

693. 
glycero-pfwsphoric acid, when daily elimination of phosphorus is excessive, 337. 
hexamethylenamine, as a urinary antiseptic, 557. 

Phosphorus=Poisoning : 

treatment of, 344. 

Phthisis : 

alcohol, of value as an accessory food and stimulant to digestion, 205. 

antipyrine, to control the fever, 462. 

arsenic, in fibroid or slowly progressing types, 351. 

calcium phosphate, 335. 

camphoric acid, to check the night-sweats, 192 

cannabis indica, as a euthanasiac, 117. 

cantharidin, (note) 605. 

cocaine, as a local application in irritated throat conditions, 126. 

codeine, to check the cough, 72. 

cod-liver oil, of service on account of food value and perhaps through some specific 

action, 388. 
creosote, acts as a stimulant expectorant, 675. 

creosote carbonate, asserted to be less injurious to the stomach than creosote, 676. 
formaldehyde, has been employed by inhalation with doubtful benefit, 689. 
gallic acid, to lessen the night-sweats, 287. 
guaiacol, as a stimulant expectorant, 677. 

heroine, perhaps the most generally useful cough sedative known, 75. 
hypophosphites, 336. 

iodine, to be used only in very chronic conditions, 376. 
prunus virginiana, used for cough, but very feeble, 478. 
sulphuretted hydrogen, an active but unpleasant expectorant, 578. 
theocol, 676. 
tuberculin, its precise value as a curative agent is uncertain, 415. 

Piles : 

See Hemorrhoids. 

Pityriasis : 

oil of cajuput, 442. 
resorcinol, 685. 

Pleurisy : 

atropine, as a circulatory stimulant in conditions of collapse, 105. 

blisters, their counter-irritant effect often of service, 603. 

gelsemium, 173. 

iodine, in chronic cases with serous effusion, 377. 

mercury, beneficial in cases with fibrinous exudate, 367. 

potassium iodide, when serous effusion is present, 377. 

poultices, the whole chest may be covered, 629. 

salicylic acid, recommended as diuretic in pleural effusion, 452. 

Pleuritic Effusions : 

See Effusion, Pleural. 



INDEX OF DISEASES ; ,.-, 

Pneumonia : 
alcohol, as a cardiac stimulani, 203. 

antipyrine, to lessen fever, Ki'J. 

arsenic, in chronic or fibrous pneumonia, 351. 
atropine, as a circulatory stimulant 104 

blisters, CAVA. 

«"»P>>or, used hypodermically is a very useful cardiac stimulani in emergenoies, 

cold-u>ater compresses, preferable ... hot applications when temperature is high, 

digitalis, as heart stimulant, especially valuable in later states 23] 

ergot, used in the early stages, 589. , - >■• 

gelsemium, 173. 

guaiacol, used as antipyretic, hut is dangerous (i77 

mercury, 367. 

musk, as a nervous stimulant in adynamic forms 1". 

naphthol, oily solution dropped into trachea (iSI ' 
ml of turpentine, as a counter-irritant application 55] 
phosphorus, for the nerve exhaustion in adynamic cases :«<) 
poultices, 629. ' 

tartar emetic, to reduce circulatory excitement 260 
theocol, 67S. 
veratrum ciride, 265. 

Poisoning : 

alcohol, as cardiac stimulant, 20 

ammonia, hypodermically, as circulatory stimulani 185 
apomorphine, as emetic, 642. 

atropine, as a respiratory and circulatory stimulani 105 
ipecacuanha, as an emetic, 491. 

mustard, a prompt and efficient but unpleasant, emetic, 496 
potassium permanganate, antidotal to alkaloids, 660 

physiological salt solution, useful to maintain circulation and increase elimination 
52o. ' 

strychnine, probably most powerful respiratory stimulant known 1 It) 
zinc sulphate, the most generally useful emetic in poisoning, 496. 

Poliomyelitis, Acute : 

See Infantile Paralysis. 
Polyuria : 

See Diabetes Insipidus. 

Post=partum Hemorrhage : 

ergot, acts by causing uterine contractions, most valuable remedy known 587 
ipecacuanha, supposed to affect coagulability of blood, 492. 

Pregnancy : 

calcium phosphate, as a prophylactic against foetal rickets, 336. 
cerium oxalate, for vomiting, 307. 
confection of senna, useful as a laxative, 507. 
ipecacuanha, for relief of vomiting, 491. 

Prolapse of Rectum : 

strychnine, 139. 

Prurigo : 

hydrocyanic acid, a local anaesthetic used to allay itching, 280. 
naphtol, used in form of soap as antiseptic, 681. 

Pruritus : 

brucine, 143. 

glycerin, when there is lack of sebaceous secretions, 626. 

hydrocyanic acid, 280. 

menthol, a useful local anossthetic, 681. 

tobacco, 175. 



746 INDEX OF DISEASES 

Prussic Acid poisoning : 

treatment of, 281. 

Pseudo=membranous Croup : 
See Croup. 

Psoriasis : 

arsenic, employed internally, 351. 

chrysarobin, one of the most efficacious remedies known for this disease, 601. 

glycerin, emollient, is excellent vehicle for more powerful drugs, 626. 

iodine, of secondary value, 378. 

oil of cajuput, stimulant and parasiticide, 442. 

phosphorus, used internally, 340. 

pyrogallol, dangerous if used too freely, 616. 

resorcinol, 685. 

thymol iodide, 387. 

thyroid extract, claimed to have a peculiar alterative effect on skin, 406. 

Psorophthalmia : 

citrine ointment, 371. 

Ptyalism : 

atropine, the most valuable internal remedy known, 105. 
tannic acid, used in solution as mouth wash, 286. 

Puerperal Convulsions : 

amyl nitrite, if used immediately after labor may cause post-partum hemor- 
rhage, 168. 
anaesthetics, 22. 
camphor, of little value, 191. 

chloral, one of the most powerful anticonvulsants known, 80. 
ethyl carbamate, as an anticonvulsant, 89. 
veratrum, 265. 

Puerperal Eclampsia : 

See Puerperal Convulsions. 

Puerperal Fever : 

digitalis, as a circulatory stimulant, 231. 

nuclein, claimed to prevent the growth of septic bacteria, 402. 
oil of turpentine, may be used both internally and externally, 551. 
streptococcus antitoxin, results have not proved encouraging, 410. 
See also Septicemia. 

Purpura Hemorrhagica: 

gelatin, acts by increasing coagulability of blood, 401. 
oil of turpentine, 551. 

Pyemia : 

alcohol, as a circulatory and general stimulant, 203. 

quinine, not probable that it exercises any direct action on pyogenic organisms, 

428. 
tincture of ferric chloride, 328. 

Pyelitis : 

buchu, a mild stimulant to the urinary mucous membranes, 546. 

cantharides, actively stimulating, to be used only in chronic cases, 605. 

copaiba, 553. 

juniper, diuretic and stimulating, used in chronic cases, 555 

methylene-blue, doubtful if of value, 439. 

salicylic acid, acts as urinary antiseptic, 452. 

turpentine, 551. 

urotropin, urinary antiseptic, especially useful in lithemic patients, 557. 

uva ursi, mildly astringent and diuretic, 547. 



INDEX OF DISEASES 747 

Pyrexia : 

See Fever. 

Pyrosis : 

bismuth, antiseptic and sedative, 306. 
manganese dioxide, 329. 

Quinsy : 
salicylates, 452. 

Rachitis : 

See Rickets. 

Remittent Fever : 

arsenic, used only when quinine not available, 3.50. 

diaphoretics, when paroxysms are close together, 561. 

quinine, must be used in full dose, 430. 

Warburg's tincture, a very powerful combination containing quinine, 436. 

Renal Calculi: 

See Calculi. 

Retention of Urine : 

strychnine, when due to atony of bladder, 139. 

Retina, Detachment of: 

dionine, 74. 

Retinitis : 

iodipin, 380. 

Rheumatic Neuralgia: 

aconite, applied locally, 273. 

potassium iodide, in subacute or chronic cases, 376. 

salicylates, the most generally serviceable remedy, 451. 

Rheumatism : 

aconite, used to produce sweat, 273. 

arsenic, in chronic cases; may be alternated with iodides, 352. 

aspirin, a form of exhibiting salicylic acid much less likely to disturb digestion, 

456. 
Burgundy pitch, as a mildly counter-irritant plaster, 610. 
carbolic acid injections, 838. 
cathartics, 500. 

cod-liver oil, useful in chronic types especially when poor nutrition, 390. 
colchicum, in those cases approaching the gouty type, 393. 
diaphoretics, to prevent muscular rheumatism following exposure, 561. 
Donovan's solution, used only in chronic cases, 371. 
guaiac, 397. 

ichthyol, mildly counter-irritant and alterative, 396. 
iodine, used externally in chronic cases, 377. 
iodoform, internally in chronic cases as analgesic, 376. 
jaborandi, to produce sweating, 567. 
magnesia, antacid and laxative, 635. 
methylene-blue , as an analgesic, 438. 
oil of cajuput, 442. 
phenocoll hydrochloride, 472. 
phenol, injected deeply, 669. 
potassium salts, antacid and increase oxidation, especially valuable in acute 

cases, 538. 
potassium iodide, a very valuable remedy in chronic cases, 376. 
pyramidon, in acute cases to relieve pain, 478. 
quinine salicylate, 430. 
salicylates, the standard remedies in all forms of rheumatism, 451. 



74S INDEX OF DISEASES 

Rheumatism (Continued): 
salipyrin, as an analgesic, 472. 

salol, not very powerful but often of service in chronic cases, 673. 
salophen, acts much like salol, 457. 

sulphur, as a laxative, also as alterative in chronic cases, 694. 
water, aids elimination of noxious materials, 526. 
xanthoxylum, 398. 

Rheumatism, Inflammatory : 

antipyrine, to relieve excessive fever, 462. 

benzoic acid, asserted to be equal to salicylic acid, 692. 

cimicifuga, an old remedy rarely employed to-day, 19 

lemon-juice, 513. 

phenocoll hydrochloride, 472. 

potassium salts, one of most valuable treatments; encourages oxidation and 

corrects systemic hyperacidity, 538. 
quinine, in very large doses, efficacious but dangerous, 429. 
salicylic acid, relieves pain and hyperpyrexia and probably has direct curative 

effect on morbid metabolism, 451. 

Rheumatoid Arthritis: 

arsenic, probably the most frequently useful remedy known, 352. 

potassium iodide, 376. 

salicylic acid, but rarely of service, 451. 

Rhinitis : 

boric acid, sedative and antiseptic local application, 698. 
camphor-mentlwl, applied locally dissolved in liquid petrolatum, 682. 
hydrastis, an excellent local remedy especially in chronic catarrhs, 595. 
ichthargan, actively germicidal, may be used in spray, 320. 
suprarenal extract, constricts the engorged blood-vessels, 245. 
See also Catarrh. 

Rhus=Toxicodendron Poisoning : 

lobelia, 171. 

Rickets : 

calcium phosphates, when there is a deficiency of lime salts in nutriment, 335. 
cod-liver oil, a valuable remedy especially in poorly nourished subjects, 390. 
phosphorus, stimulates the growth of bone, 340. 

Rigidity of Os Uteri : 

belladonna, applied locally, 104. 

Round=Worms : 

azedarach, used but comparatively little, 647. 

chenopodium, a useful remedy, 643. 

oil of turpentine, 646. 

santonin, one of the most active drugs against this parasite, 640. 

spigelia, safe and efficient, 643. 

Salivation : 

See Ptyalism. 

Scabies : 

glycerin, as an emollient vehicle, 626. 

resorcinol, somewhat antiseptic, 685. 

sulphur, the most frequently employed remedy, 694. 

Scarlet Fever: 

alcohol, as a circulating stimulant for threatened collapse, 203. 
ammonia, rapidly acting cardiac stimulant, 185. 
antipyrine, to reduce hyperpyrexia, 462. 

atropine, has no specific action, as formely believed, but is valuable as a stimulant, 
105. 



INDEX OF DISEASES 749 

Scarlet Fever (Continued) : 
capsicum, as a local application for the accompanying sore throai 183 
hydrogen dioxide, used as antiseptio application to the throai 8 
streptococcus antitoxin, for secondary infections, especially of throai 11 1 

urotropin, probably of use as preventive of nephritis, .w. 

Sciatica : 

acetopyrin, as an analgesic, 166. 

guaiac, 529. 

iodides, of value in subacute rheumatic eases, 376. 
salicylates, the most useful remedy in rheumatic cases, 451, 
aaloquinine, analgesic and antirheumatic, 437. 

Scleritls : 
iodipin, 380. 
physosngmine, 152. 

Scleroderma : 
thiosvnamine, 398. 

Scrofulosis : 

alcohol, as an accessory food, 205. 

calcium phosphate, 334. 

calx sulphurata, internal remedy for scrofulous glands, 694. 

cod-liver oil, to improve nutritive condition, 390, 

gold and sodium chloride, 373. 

gold oxide, 373. 

ichthalbin, a derivative of ichthyol suitable for internal use, 3<)(i. 

iodine, used internally for glandular enlargements, especially when no suppura- 
tion, 378. 

phosphoric acid, largely used but, of little value, X'A. 

syrup of ferrous iodide, combines alterative action of iodine with tonic effeel of 
iron, 328. 

Scurvy : 

lemon-juice, a specific; the only remedy of value, 513. 

Seat-Worms : 

forced enemata, 501. 

naphtha lin, given by injection, 080. 

quassia, probably the most generally useful remedy; use in en< ma, 176 

vinegar, 290. 

Seborrhcea : 

arsenic, internally when of neurotic origin, 351. 
glycerin, externally to soften the skin, 626. 
resorcin, stimulant and antiseptic, 685. 

Seminal Emissions : 

See Spermatorkhcea. 

Septicemia : 
antitoxin, has not given brilliant results, 110. 
colloidal silver, its value is problematical, 320. 
formaldehyde, intravenous injections of no service, (><)(). 
ichthargan, used hypodermic-ally, but no positive evidence of value, 320. 
quinine, perhaps useful as antipyretic, has no specific action, 428. 

Serous Diarrhoea : 

See DlARRHCEA. 

Sexual Excitement : 

camphor, a feeble sedative, 191. 
hops, frequently employed but of little use, 18. 

hyoscine kydrobromate, one of the most reliable sedatives known for this con- 
dition, 111. 



750 INDEX OF DISEASES 

Sexual Excitement (Continued) : 
monobromated camphor, 161. 
potassium bromide, a very valuable remedy, 158. 
See also Nymphomania. 

Shock : 

See Collapse. 

Sick Headache: 

antacids, to correct acidity of stomach, 632. 

aromatic spirit of ammonia, the most generally useful antacid, 632. 

magnesia, laxative and antacid, 635. 

Sick Stomach : 

creosote, local anaesthetic and antiseptic, 675. 
ipecacuanha, as a gastric stimulant in atonic nausea, 491. 
See also Vomiting. 

Silver-Nitrate Poisoning : 

treatment of, 318. 

Singultus : 

See Hiccough. 

Sinking-Spells : 

See Syncope. 

Skin Diseases: 

aluminum hydroxide, mildly astringent, 292. 

arsenic, used internally in chronic conditions, 351. 

chalk, as a protective and desiccant, 637. 

chrysarobin, an excellent stimulating application, especially in psoriasis, 601. 

citrine ointment, 371. 

cod-liver oil, used internally to improve nutrition, 390. 

Donovan's solution, used internally as an alterative, 371. 

gold iodide, 373. 

ichthyol, a local remedy of wide applicability, 396. 

iodine, occasionally used as an antiseptic, 378. 

magnesia, as a laxative antacid, 635 

naphtol, as an antiseptic soap, 681. 

nitro-hydrochloric acid, for its stomachic effect, 333. 

oil of cajuput, stimulating and parasiticide, 442. 

ointment of oxide of mercury, 371. 

ointment of zinc oxide, 309. 

phosphorus, internally in various chronic conditions, 340. 

resorcinol, 685. 

salicylic acid, 454. 

sulphur, used both internally and externally, 694. 

tar, 576. 

thyroid extract, especially in psoriasis and keloid, 406. 

vinegar, as a sedative astringent in acute inflammations, 290. 

zinc oxide, a widely useful astringent, 308. 

Sleeplessness : 

bromipin, a preparation of bromides, 160. 

bromolein, 160. 

cannabis indica, 117. 

chloral, the most powerful hypnotic known in nervous insomnia, 79. 

chloralformamid, less powerful but less depressant than chloral, 90. 

chloralose, uncertain in its effects, 91. 

chhretone, feeble and uncertain, 92. 

dormiol, of moderate power in insomnia of nervous origin, 90. 

hedonal, sometimes of use in cases of not great severity nor associated with pain, 

90. 
hyoscine hydrobromide, especially serviceable in insomnia of insanity or delirium, 

110. 



IN DUX OF DISEASES 7. r ,l 

Sleeplessness (Continued): 

isopral, as actively depreasanl as chloral hydrate, over which it baa no advan- 
tages, 90. 

opium chiefly of value in insomnia due to pain, 64 

paraldehyde, a safe and powerful remedy in sleeplessness not associated with 
pain, 88. 

potassium bromide, comparatively feeble as direct somnifacient, bul useful in 
cases where wakefulness is caused by stimuli from without, I ,. 

sulpkones, including sulphonal and trional valuable in nervous insomnias, SI. 

urethan, a safe and moderately active remedy in nervous insomnia, 89. 

veronal, 91. 

Smallpox : 

ichthyol, employed locally to prevent pitting, 396. 
opium, to sustain system by blunting sensibilities, 65. 
thiosinamine, to cure the scars after smallpox, 398. 

Snake-poisoning : 

alcohol, of value as circulatory stimulant, but is not a specific as sometimes 

believed, 204. 
ammonia, a useful heart stimulant, inject hypodermically, 185. 
antitoxin, acts specifically in bites from certain varieties of snakes, 413. 
potassium permanganate, as a local antidote; should be injected into wound, 660. 

Sore Nipples : 

See Nipples, Sore. 

Sore Throat : 

acacia, dissolved in the mouth is very soothing in acute inflammations, 617. 

alum, as an astringent, not fitted for gargle, 292. 

carbolic acid, in ulcerated or diphtheritic sore throat as an antiseptic, 669. 

chlorine water, as a disinfectant gargle in violent infections, 659. 

cocaine, applied locally as vasoconstrictor and anaesthetic, 126. 

creosote, locally as antiseptic, 676. 

mercury, internally as antiphlogistic, 367. 

phenol injections, 669. 

potassium chlorate, a very valuable astringent in not too acute inflammations, 541. 

salicylates, specific in tonsilitis and rheumatic angina, 452. 

silver nitrate, sedative astringent and germicidal, 316. 

sumach berries, make an excellent astringent gargle, 288. 

tannic acid, applied by swab or as a gargle, 286. 

thymol, as antiseptic, 683. 

Spasms : 

aconite, not generally useful, 273. 

amyl nitrite, a very powerful and rapidly acting but fugacious relaxant, 167. 

anaesthetics, in severe hysterical or spinal convulsions, 22. 

asajetida, when due to hysteria, 17. 

atropine, in local spasms especially of involuntary muscles, 104. 

chloral, in all forms of violent generalized convulsions a valuable remedy, 80. 

hyoscine, in asthma, whooping-cough, and similar disorders, 111. 

lobelia, in spasms of the bronchial muscles, 171. 

oil of cajuput, recommended in intestinal spasm, 442. 

opium, especially in cerebral or painful spasms, 64. 

potassium bromide, one of the most valuable remedies in spinal and epileptic 

convulsion, 157. 
sulphonal, a feeble anticonvulsant, 84. 

Spermatorrhoea : 

antipyrine, 463. 

chloral, useful in spasmodic types, 80. 

digitalis, asserted to be actively anaphrodisiac. 232. 

hyoscine hydrobromide, one of the most valuable remedies known, 111. 

monobromated camphor, 161. 

potassium bromide, a very useful sexual sedative, 157. 

sulphonal, 84. 

turpentine, in cases with marked atony, 551. 



752 INDEX OF DISEASES 

Spinal Congestion : 

ergot, 589. 

Spinal Depression : 

strychnine, 138. 

Spinal Scleroses : 

gold and sodium chloride, beneficial results have been claimed for it, 373. 
silver nitrate, an old remedy of doubtful value, 317. 

Spleen, Enlargement of : 

ergot, contracts vessels, useful in cases of chronic congestion, 589. 
potassium bromide, in post-malarial spleens, 158. 

Spongy Gums : 

tannic acid, 286. 

Sprains : 

arnica, as a stimulant, application, 610. 

camphor, as a counter-irritant, 191. 

dilute acetic acid, a sedative, astringent lotion, 290. 

ichthyol, 396. 

lead water, a frequently employed sedative embrocation, 294. 

Status Epilepticus : 

amyl nitrite, 167 

Stomach, Diseases of: 

See Cancer of Stomach, Dyspepsia Gastritis etc. 

Stomatitis : 

boric acid, a large crystal of borax allowed to dissolve in the mouth is an excel- 
lent treatment, 698. 
phenol, the ulcers to be touched with a concentrated solution in glycerin 669. 
potassium chlorate, employed both as a mouth wash and taken internally, 541 . 
sodium chlorate, (note) 541. 
thymol, useful as antiseptic on account of pleasant taste, 683. 

Stricture : 

anaesthetics, in spasmodic stricture of oesophagus, 22. 

belladonna, in spasmodic stricture of either urethra or bowels, 104. 
thiosinamine, asserted to be useful in true urethral stricture, 398. 

Strychnine=Poisoning : 

amyl nitrite, use by inhalation or hypodermicallv to produce immediate relaxa- 
tion, 168. 
bromides, among the most valuable remedies we have, 157. 
chloral, a very useful spinal depressant, 80. 
physiological salt solution, to aid in elimination of poison, 527. 
physostigma, a remedy of only secondary power, 151 
treatment of, 142. 

Suffocative Catarrh : 

apomorphine hydrochlorate, as an emetic to evacuate exudate, 495. 
treatment of asphyxia in, 571. 

Sulphone=Poisoning : 

treatment of, 87. 

Summer Complaint : 

See Cholera Infantum. 

Sunburn : 

dilute acetic acid, a valuable sedative astringent, 290. 



INDEX OF DISEASES 

Suppressed Menstruation : 
See AiuDNOBRBa v. 

Suppression of Urine : 
calotnel, one of the mos1 powerful diureties known in parenchymatous nephritis 

jaborandi, given in small doses sometimes of servioe, 587. 

water, when suppression dependent on acute irritation of kidneys, 526 

Sweating, Excessive : 

See Hyperidkosis. 

Sycosis : 

opsonic treatment, 415. 

Syncope : 

alcohol, a rapidly acting cardiac stimulant, 204. 

ammonia, irritant action of vapors on mucous membrane of nose acts reflexly 

as stimulant, 185. 
amyl nitrite, a dangerous remedy, as the slightest, overdose is depressant, 168. 
digitalis, give hypodermically in large doses, 230. 
ether, 30. 

Synovitis : 

phenol injections, 669 

Syphilis : 

berberix, 477. 

calcium phosphate, recommended in syphilitic periostitis, also in gumma, 336. 

cod-liver oil, in the cachexia of tertiary stage, 390. 

copper sulphate, as adjunct to mercury, 310. 

difluor-diphenyl, as a local application to ulcerating lesions, 659. 

gold and sodium chloride, in sclerosis of nervous system, 373. 

gold iodide, 373. 

guaiac, a remedy of secondary importance, may be used as adjunct, 397. 

ichthalbin, 396. 

iodipin, has same effect as iodides, but acts more slowly and persistently, 380. 

iodoform, used internally especially when "night-pains " 382 

iodol, 386. 

mercury, especially useful in early stages, but a specific in all forms, 367. 

nitric acid, 332. 

nitro-hydrochloric acid, to improve digestion, 333. 

potassium iodide, a specific, employed most frequently in tertiary stage, 376 

sarsaparilla, perhaps of service as adjunct, 397. 

sulphur, natural sulphur-waters, recommended in chronic syphilis, (id I. 

thiosinamine, as a local application in syphilitic skin lesions, 398. 

thymol iodide, as a dusting powder for local lesions, 387. 

Tapeworm : 

aspidium, one of the best remedies against tapeworm, but is poisonous, 645. 

chloroform, probably of little value, 34. 

cusso, efficient and harmless, 645. 

ether, of only secondary value, 30. 

kamala, 647. 

large enemata, 501. 

oil of chenopodium, an active anthelmintic, 643. 

oil of turpentine, 646. 

pepo, the safest and one of the most powerful tanicides, 645. 

pomegranate, efficient, but poisonous in overdose, 646. 

thymol, 646. 

Tetanus : 

amyl nitrite, to allay spasm which threatens immediate death, although power- 
ful too fugacious for constant use, 168. 
48 



754 INDEX OF DISEASES 

Tetanus (Continued): 
antipyrine, 463. 

antitoxin, is of service as a prophylactic, 410. 
cannabis irvdica, 117. 

chloral, one of the most generally serviceable remedies known, 80. 
ethyl carbamate, 89. 

phenol, hypodermic injections have been asserted to act very favorably, 668. 
physostigma, useful as adjunct, too feeble to be relied upon, 151. 
potassium bromide, probably the best single remedy, must be used in large doses, 
157. 

Tinea Capitis : 

acetozone, as a local germicide, 663. 

lime-water, valuable as a sedative application, 637. 

resorcinol, stimulant and parasiticide, 685. 

ToadstooI=Poisoning : 

See Muscarine Poisoning. 

Tonsillitis : 

capsicum, applied locally with a swab, 483. 
guaiac, used internally, 397. 
ichthargan, as a local germicidal astringent, 320. 
See also Sore Throat. 

Toothache : 

oil of cloves, saturated pledget of cotton placed in cavity, 481. 

Torticollis : 

atropine, injected deeply into muscle, 104. 
hyoscine, usually fails, 111. 

Trachoma : 

ichthargan, 320. 

Trichiniasis : 

picric acid, 647. 

Trismus Nascentium : 

Calabar bean, 151. 
chloral, 79. 
physostigma, 151. 

Tuberculosis : 

arsenic, as a reconstructive alterative especially in chronic cases, 351. 
cacodylic acid, a mode of exhibiting arsenic, 359. 
camphoric acid, for the relief of night sweats, 192. 
cantharidin, (note) 605. 

cinhamic acid, in pulmonary tuberculosis probably useful as a stimulating ex- 
pectorant, 693. 
cod-liver oil, one of the most valuable drugs known to improve nutrition, 390. 
colloidal silver, 320. 
dionine, for relief of cough, 73. 
fluoroform, 659. 

guaiacol, as a stimulant expectorant, 677. 
heroine, as a local anaesthetic in laryngeal tuberculosis, 75. 
iodoform, as a topical application in various forms of local tuberculosis, 383. 
lactic acid, as a caustic in laryngeal tuberculosis, 616. 
lecithin, asserted to exercise a beneficial effect on nutrition, 399. 
nucleins, 401. 
opsonic treatment, 415. 
pyramidon, to reduce excessive fever, 473. 
tannoform, as an antiseptic astringent in diarrhoea, 290. 
See also Abscesses and Phthisis. 



INDEX OF DISEASES 755 

Tympanites : 
aromaHcs, 479. 

asafetida, especially valuable in debilitated subjeots, 17. 
physostigma, a direct stimulant to intestinal muscle fibres, 151. 

Typhoid Fever: 

For methods of controlling temperature sec under Fey Kit. 

For treatment of hemorrhage see under IIkmokkii \cr, I'ltmi the How i i - 

Ocetozone, as an intestinal antiseptic, 663. 

alcohol, an essential part of the treatment; aids digestion, acts as food, and stimu- 
lates circulation, 203. 

beta-naphthol, lessens intestinal fermentation by its antiseptic effects, 681. 

caffeine, 217. 

camphor, hypodermically in threatening collapse, a powerful heart stimulant, 
101. 

chlorine, as intestinal antiseptic, 659. 

creosote, as intestinal antiseptic, 675. 

digitalis, claimed to act as antipyretic as well as cardiac stimulant, 231 . 

guaiacol, as an antipyretic is dangerous, 677. 

hydrochloric acid, of little benefit, 331. 

jaborandi, 567. 

musk, in conditions with low muttering delirium a very valuable remedy, 15. 

naphthalin, 6S0. 

oil of turpentine, best remedy for tympanites, acts as an intestinal antiseptic and 
carminative, 550. 

salol, probably most effective intestinal antiseptic, 673. 

sulphur, 694. 

suprarenal extract, to check hemorrhage from bowels, 245 

thymol, of little value, 683. 

Typhus Fever: 

alcohol, useful as an accessory food as well as circulatory stimulant, 203. 

antipyrine, to reduce excessive pyrexia, 462. 

atropine, as a circulatory stimulant, 105. 

chloral, as a cerebral sedative in delirious cases, 79. 

chlorine water, 659. 

Ulcer of Cornea : 

See Corneal Ulceu. 

Ulceration of the Bowels : 

copper sulphate, 310. 
oil of turpentine, 550. 

Ulcers : 

acetozone, 663. 

alum, astringent, used when excessive secretions, 292. 

black wash, in syphilitic ulcers, 371. 

Canquoin's paste, as a caustic in syphilitic growths, 614. 

chalk, as a desiccant and protective, 637. 

chloral, anaesthetic and antiseptic, 80. 

chloretone, somewhat antiseptic and locally ainesthetic, 92. 

chlorine water, a stimulant disinfectant application, 659. 

copaiba, in chronic ulcers of the stomach, 553. 

copper sulphate, in indolent ulcers especially of mucous membranes, 310. 

creosote, as a disinfectant in foul ulcers, 676. 

escharotics, to destroy exuberant granulations, 611. 

ichthargan, a silver germicidal preparation, 320. 

ichthyol, 396. 

iodoform, a desiccant, alterative, and antiseptic, 382. 

lime-water, 803. 

mezereon, 397. 

nitric acid, actively caustic, 615. 

phenol, an active germicide, 669. 



756 INDEX OF DISEASES 

Ulcers {Continued): 

■potassium permanganate, antiseptic and cleansing, used where much suppuration, 

660. 
red mercuric oxide, 370. 
silver nitrate, mildly stimulant and actively germicidal, used especially to destroy 

exuberant granulations, 316. 
solution of mercuric nitrate, as a caustic, 614. 
sulphuric acid, a dilute solution stimulant and astringent, 330. 
tannic acid, to lessen excessive secretion on old ulcers, 286. 
tannoform, supposed to be both antiseptic and astringent, 290. 
thyroid extract, 406. 
yellow wash, in syphilitic ulcers, 371. 
zinc oxide, used as desiccant and astringent dusting powder, 308. 

Uncinariasis : 

thymol, 646. 

Uremia : 

chloral, to control convulsions, 80. 

elaterin, a hydragogue purgative believed to eliminate urea through the bowels, 519. 

jaborandi, as a diaphoretic, 567. 

nitroglycerin, used to overcome spasms, 168. 

opium, used, as anticonvulsant and diaphoretic, but dangerous on account of 

effect on secretion of urine, 66. 
quebracho, to combat dyspnoea, 180. 
water, of value to flush out the system, 526. 

Urethral Fever: 

aconite, 273. 

bromides, lessens irritability of genital system, 157. 

Urethral Spasm : 
belladonna, 104. 

Urethritis : 

acetanilid, a suspension may be used locally, 469. 
copper sulphate, 310. 

silver nitrate, actively astringent and germicidal, 316. 
See also Gonorrhoea. 

Uric Acid Calculus and Gravel : 

benzoic acid, one of the most generally useful remedies known, 692. 

piperazine, useful in gravel, 543. 

potassium salts, of service as prophylactic, 538. 

soda, inferior to potash, 634. 

Uric Acid Diathesis: 

benzoic acid., a useful remedy, 692. 

lithium, much employed but of uncertain value, 543. 

potassium salts, increase oxidative processes of body, frequently of much service- 

538. 
sodium salts, 634. 

sodium phosphate, as a laxative, 511. 
water, aids elimination of poisonous material, 526. 

Urticaria : 

arsenic, in chronic forms, 351. 

cimicifuga, acts almost specifically in neurotic cases, 19. 

emetics, when due to gastric irritation, 487. 

ichthyol, as a local application, 396. 

menthol, as a local application to lessen itching, 682. 

Uterine Inertia: 

ergot, to be used very cautiously on account of danger of uterine spasm, 586. 
quinine, in full dose sometimes of service, 426. 






INDEX OF DISEASES 757 

Uterus, Cancer of: 
chloral, as n local anaesthetic and antiseptic, 80 
cotton-roof, to arrest the hemorrhage, 598 
heroine, as a local ansBathetio. 7"). 
iodoform, applied locally to allay pain. 384. 

Uterus, Fibroid Tumors of: 

cotton-mot, to allay hemorrhage or other symptoms. ">!>n. 
crootin, has been administered hypodermically, 588. 
kydrastis, to lesson hemorrhage, 595. 

Uterus, Subinvolution of: 

ergot. 588. 

Uveitis : 

dionine, increases lymphatic circulation in eye, 74. 
salicylic acid, 152. 

Vaginismus : 

piperine, 483. 

Vaginitis : 

acetunilnl, used locally in a suspension, stimulant antiseptic, 469. 

bismuth oxyiodogallate, used in suppository, antiseptic and sedative, 307. 

grindelia, 577. 

kydrastis, influences mucous membrane directly, 595. 

ichthargan, a germicidal silver preparation, 320. 

Valvular Heart Disease: 

See Endocarditis. 
Venereal Ulcers : 

See Chancres and Chancroids. 

Venereal Warts : 
nitric acid, 332. 

Veratrum=Viride Poisoning : 

alcohol, as a heart stimulant, 204. 
treatment of, 265. 

Vomiting : 

aconite, locally stimulant and anesthetic, especially valuable in pregnancy, 274. 

bismuth subnitrate, sedative, astringent, and antiseptic, 306. 

bromides, in reflex vomiting from uterine disturbances, 157. 

cerium oxalate, believed to have a specific action especially in vomiting of preg- 
nancy, 307. 

chloretone, for its local anesthetic influence, 92. 

cocaine, paralyzes the sensory nerves of stomach, 126. 

creosote, antiseptic and local anesthetic, 675. 

hydrastis, stomachic, 595. 

ipecacuanha, in atonic conditions, especially in pregnancy, 491. 

lime-water, to render milk more easily digested, 637. 

opium, one of the best remedies we have, benumbs vomiting cent re; may Ik: 
given per rectum, 65. 

orexin, stimulant to gastric mucosa, especially recommended after anesthesia 
and in pregnancy, 478. 

phenol, antiseptic and locally anesthetic, often of great service in gastritis, (ids; 

prussic acid, local anaesthetic, 280. 

treatment of, 488. 

Warts: 

nitric acid, one of the most generally useful caustics, 332. 

papain supposed to dissolve them by a process similar to digestion, 651. 



758 INDEX OF DISEASES 

White Swelling: 

See Joints, Inflammation of. 

Whooping=Cough : 

antipyrine, of some value as antispasmodic, 463. 

antitussin, 659. 

aristochin, a synthetic quinine derivative, 436. 

arsenic, 352. 

asafetida, antispasmodic and expectorant, 17. 

atropine, a valuable remedy on account of antispasmodic action, 104. 

bromoform, doubtful if it possesses any virtue not found in bromides, 160. 

campfior, its use has largely passed out of vogue, 191. 

chloral, useful temporarily to check spasms, 80. 

conium, an unreliable remedy, 178. 

euquinine, probably less efficient than quinine, 43(>. 

gelsemium, 173. 

grindelia, as an expectorant, 577. 

heroine, as a cough sedative, 75. 

hyoscine, for its antispasmodic effect, 11. 

quinine, seems to act specifically, perhaps exercises antiseptic effect, 432. 

thyme, 683. 

Winter Cough : 

See Bronchitis. 

Worms : 

See Round-Worms and Tapeworms. 

Wounds : 

acetanilid, as antiseptic dusting powder, of secondary value, 469. 

alcohol, actively antiseptic and sedative, especially used as a dressing, 206. 

boric acid, feebly antiseptic, 698. 

chloretone, a locally anaesthetic and somewhat antiseptic dusting powder, 92. 

corrosive sublimate, as a germicide, 655. 

escharotics, in poisoned wounds, as bites, or when seriously infected, 611. 

formaldehyde, powerfully disinfectant but too irritant for ordinary uses, of service 

when severe infection, 689. 
hydrogen dioxide, cleansing on account of its oxidizant action, also antiseptic, 662 
iodoform, desiccant anesthetic and slightly antiseptic, 382. 

orthoform, useful in painful wounds, local anesthetic, and somewhat antiseptic, 52. 
phenol, actively bactericidal, 669. 

potassium permanganate, oxidizant and disinfectant, 660. 
protargol, a germicidal silver preparation, 321. 
quinine, (note) 432. 

thymol iodide, a useful desiccant and antiseptic dusting powder, 387. 
volatile oils, (note) 479. 



GENERAL INDEX 



Abies balsamea, 548 
excelsa, 610 

A. B. S. pill, 505 
Absolute acetic acid, 290 
alcohol, 192 

Absorbent cotton, 598 
Absorbents, 652 
Acacia, 617 

catechu, 288 

Senegal, 617 
A. C. E. mixture, 41 
Aceta, 3 
Acetanilide, 466 

poisoning, 469 
Acetanilidum, 466 
Acetic acid, 290 

ether, 19 

poisoning, 290 
Acetonechloroform, 91 
Acetopyrine, 466 
Acetozone, 662 
Acetphenetidin, 470 
Acetphenetidinum, 470 
Acetum opii, 58 

scillse, 528 
Acetylparamidophenyl, 

457 
Acetylquinine, 436 
Acetyl-salicylic acid, 456 
Acid potassium oxalate, 

685 
Acidum aceticum, 290 

aceticum dilutum, 
290 

aceticum glaciale, 
290 

benzoicum, 691 

boricum, 695 

camphoricum, 192 

cinnamicum, 693 

citricum, 512 

gallicum, 287 

hydriodicum dilu- 
tum, 374 

hydrobromicum dilu- 
tum, 154 

hydrochloricum, 331 

hydrochloricum dilu- 
tum, 331 

hydrocyanicum, 276 

hydrocyanicum dilu- 
tum, 276 

hypophosphorosum, 
336 

hypophosphorosum 
dilutum, 336 



Acidum lacticum, 616 
nitricum, 330 
nitricum dilutum, 330 
nit ro-hydrochlori- 

cum, 333 
nit ro-hydroclilnri- 
cum dilutum, 333 
oleicum, 622 
oxalicum, 685 
phosphoricum, 334 
phosphoricum dilu- 
tum, 334 
picrum, 647 
salicylicum, 446 
stearicum, 622 
sulphuricum, 330 
sulphuricum aromat- 
ic um, 330 
sulphuricum dilutum, 

330 
sulphurosum, 694 
tannicum, 284 
tartaricum, 511 
trichloraceticum, 615 
Aconine, 267 
Aconite, 266 

poisoning by, 274 
Aconitina, 267 
Aconitine, 267 
Aconitum, 266 

anthora, (note) 266 
cammarum, (note) 

266 
ferox, (note) 266 
fischeri, (note) 266 
japonicum, (note) 

266 
lycoctonum, (note) 

266 
napellus, 266 
neomontanum, 

(note) 266 
paniculatum, (note) 

266 
tauricum, (note) 266 
variabile, (note) 266 
Acrinyl sulphocyanate, 

607 
Actol, 319 
Adeps, 622 

benzoinatus, 622 
lanse, 622 
Adeps lanae hydrosus, 622 
Adjuvant elixir, 619 
Adonidin, 251 
Adonis vernalis, 251 



Adrenalin, 242 
Adrenals, 'ill 

.MiIkt, 26 

aceticus, 19 
^Ethylis ohloridum, 35 

carbamas, 89 
African pepper, 183 
Agaric, 290 

acid, 291 
Agaricin, 291 
Agaricinic acid, 291 
Age in relation to dose, 7 
Agropyron repens, 548 
Agurin, 532 
Airol, 307 
Albargin, 319 
Alcohol, 192 

absolutum, 192 

dilutum, 192 

poisoning, 207 
Alexandria senna, 506 
Allis inhaler, 43 
Allspice, 482 

Allyl-sulphocarbamide, 
398 

sulpho-urea, 398 
Aloe, 505 

purificata, 505 
Aloes, 504 
Aloin, 505 
Aloinum, 505 
Alpha-eucaine, 51 
Alpha-naphthol, 680 
Alterative diuretics, 546 
Alteratives, 338 
Althaea, 620 

officinalis, 620 
Alum, 291 

curd 292 

dried, 292 
Alumen, 292 

exsiccatum, 292 
Aluminii hydroxidum, 
292 

sulphas, 292 
Aluminum, 291 
Aluminum hydroxide, 
292 

sulphate, 292 
American silver fir, 548 
Amido-camphor, (note) 

187 
Aminoform, 556 
Ammonia, 182 

poisoning, 186 

water, 183 

759 



760 



GENERAL INDEX 



Ammoniac, 577 
Ammoniacum, 577 
Ammoniated mercury, 
360 

tincture of guaiac, 
397 

tincture of valerian, 
15 
Ammonii benzoas, 691 

bromidum, 154 

carbonas, 183 

chloridum, 183 

iodidum, 374 

salicylas, 446 

valeras, 16 
Ammonium, 182 

benzoate, 691 

bromide, 154 

carbamate, 182 

carbonate, 182 

chloride, 183 

hydroxide, 182 

ichthyo-sulphate, 395 

iodide, 374 

picrate, 647 

salicylate, 446 

valerate, 16 

valerianate, 16 
Amorphous aconitine, 
267 

aspidospermine, 179 
Amygdala amara, 282 
Amygdalin, 478 
Amylene chloral, 90 
Amyl nitrite, 161 
Amyl salicylate, 456 
Amylis nitris, 162 
Amylum, 619 
Anesthesia, practical, 37 

accidents in, 46 

after-effects of, 49 

local, 51 
Anesthetics, 21 

administration of, 43 
Anarcotine, 72 
Andira araroba, 600 
Angelic acid, 17 
Animal charcoal, 652 
Anise, 480 
Antacids, 631 
Anthelmintics, 639 
Anthemis, 483 

nobilis, 483 
Anthrarobin, (note) 600 
Anthraquinone deriva- 
tives, 503 
Antidiphtheric serum, 

408 
Antifebrin, 466 
Antimonial wine, 257 
Antimonii et potassii tar- 

tras, 257 
Antimony, 257 

and potassium tar- 
trate, 257, 573 

poisoning by, 260 



Antinosine, 387 

Antiperiodics, 419 

Antipyretics, 444 

Antipyrinse acetyl-salicy- 
las, 466 

Antipyrine, 457 
poisoning, 464 
salicylate, 472 

Antipyrina, 457 

Antipyrylurea, 472 

Antiseptics, 653 

Antispasmodics, 14 

Antitoxins,. 407 

Antitussin, 659 

Antivenin, 413 

Apiol, 580 

Apium petroselinum, 580 

Apocodeine, 501 

Apocynein, 236 

Apocynin, 236 

Apocynum, 236 

cannabinum, 236 

Apomorphinae hydrochlo- 
ridum, 493 

Apomorphine hydrochlo- 
ride, 493, 573 

Apothecaries' measure, 
706 

weights, 706 

Appendix, 706 

Aqua ammoniae, 183 

ammonia fortior, 183 
anisi, 480 
camphorae, 187 
chloroformi, 30 
cinnamoni, 480 
creosoti, 674 
foeniculi, 480 
hamamelis, 289 
hydrogenii dioxidi, 

661 
menthae piperita, 480 
menthae virdis, 480 

Aquae, 2 

Arabin, 617 

Araroba, 600 

Arbutin, 546 

Arctostaphylos uva ursi, 
546 

Argenti acetas, 319 
casein, 320 
citricum, 319 
cyanidum, 276, 313 
lactas, 319 
nitras, 313 
nitras dilutus, 313 
nitras fusus, 313 
oxidum, 313 
sulphophenas, 319 

Argentol, 319 

Argentum, 312 
solubile, 320 

Argol, 511 

Argonin, 320 

Argyria, 313 

Argyrol, 319 



Aristochin, 436 
Aristol, 386 

Aristolochia reticulata, 
448 

serpentaria, 484 
Arnica, 609 

montana, 609 
Arnicine, 609 
Aromatic bitters, 483 

elixir, 480 

fluid extract, 480 

fluid extract of cas- 
cara sagrada, 507 

oils, 478 

powder, 480 

spirit of ammonia, 
183 

sulphuric acid, 330 

syrup of rhubarb, 504 

tincture of rhubarb, 
504 
Aromatics, 478 
Arsenic, 346 

antidotes, 356 

as a caustic, 613 

-eating, 350 

iodide, 346 

poisoning, acute, 352 
chronic, 356 

post-mortem imbibi- 
tion 358 

trioxide, 346 
Arsenical paper, com- 
pound, 572 

solution of lithium, 
543 
Arseni iodidum, 346 

trioxidum, 346 
Arsenous anhydride, 346 
Art of prescribing medi- 
cines, 8 
Artemisia pauciflora, 639 
Artificial camphor, 548 

respiration, 48 
Asafetida, 16 
Asafcetida, 16 
Asagraea officinalis, 266 
Aspidin, (note) 644 
Aspidium, 643 

spinulosum, (note) 
643 
Aspidosamine, 179 
Aspidosperma, 179 

quebracho-bianco, 
179 
Aspidospermatine, 179 
Aspidospermine, 179 
Aspirin, 456 

Astragalus gummifer, 618 
Astringents, 283 
Atomization, 5 
Atoxyl, 359 
Atropa belladonna, 94 
Atropina, 95 
Atropinae sulphas, 95 
Atropine, 95 



GENEB \i. i\im \ 



761 



Atropine, poisoning by, 

107 
sulphate, 05 
Ami el Bodii chloridutn, 

372 

Ava, ">.").") 

Aiedarach, 647 

Baking soda, 632 
Halm of Gilead, -".IS 
Balsam of Peru, 577 

of Tolu, 577 
Balsamum peruvianum, 
577 

tolu tan um, 577 

traumaticum, (i!):i 
Banks oil, 388 
Barbadoes aloes, 504 
Barbaloin, 505 
Barberry, 477 
Barley, 620 

water, 020 
Barosina betulina, 546 
Basha m's mixture, 324 
Basilicon ointment, 548 
Bassorin, 618 
Bearberry, 546 
Beech wood creosote, 674 
Belladonna, 94 

leaf, 94 

plaster, 95 

poisioning, 107 

root, 94 
Belladonna folia, 94 

radix, 94 
Benzaconine, 267 
Benzaldehyde, 282 
Benzaldehydum, 282 
Benzoic acid, 690 
Benzoin, 690 
Benzoinated lard, 622 
Benzoinum, 690 
Benzosulphinide, 627 
Benzoyl-acetyl-peroxide, 

662 
Benzoyl quinine, 436 
Benzozone, 662 
Berberine, 592 
Berberis, 477 

aquifolium, 477 

vulgaris, 477 
Bertoni's ether, (note) 161 
Beta-eucaine, 51 
Beta-naphthol, 680 
Beta-naphthol-ether sali- 
cylate, 681 
Beta-oxysantonin, 808 
Betol, 681 

Bichloride of mercury, 360 
Bile, 508 

effects of drugs on, 
514 
Biniodide of mercury. 655 
Bismuth, 304 

and ammonium ci- 
trate, 304 



Bismuth citrate, 30 1 

oxyiodogallate, 305 
poisoning, 305 
aubcarbonate, 30 I 
BubgaUate, 304 
subnitrate, 30 1 

subsalicylate, .1(1 I 

Bismuthi oitras, 30 i 

et ammoiiii citras, 

:;nl 
Btibcarbonas, 304 
Bubgallas, 304 
Bubnitras, ■'!<> t 
subsalicylas, 304 

Bisulphites, 695 

Hitter almonds, 282 
cucumber, 516 

Hitters. 176 

Black draught, 500 

ginger, 482 

haw, 581 

manganese oxide, 32S 

mustard, 607 
Black pepper, 482 

wash, 371 
Blackmail's disinfectant , 

(note) SIT) 
Blaud's pills, 323 
Bleaching powder, 656 
Blisters, 604 
Bloodroot, 577 
Blue mass, 360, 513 

ointment, 360 

stone, 310 
Boletus, 290 

laricis, 290 
Bolivian coca, 117 
Boneblack, 652 
Bonjean's ergotin, 583 
Boracic acid, 695 
Borax, 695 
Boric acid, 695 
Borneo comphor, (note) 

187 
Bornylamin, (note) 187 
Boroglycerin, 695 
Bos taurus, 508 
Bougies, 5 
Brandy, 192 
Brassica alba, 607 

nigra, 607 
Brayera, 645 
Bread-and-milk poultice, 

629 
Bromal hydrate, 161 
Bromated camphor, 161 
Bromides, 153 
Bromine, 615 

as a disinfectant, 657 
Bromipin, 160 
Bromism, 159 
Bromoform, 160 
Bromoformum, 160 
Bromolein, 160 
Bronium, 615 
Broom plant, 248 



Brown mixture, 619 

sugar, 502 

Brucine, 131, I i .: 

nitrate, I I . 
sulphate, I I.; 

Bubonic plague serum 

112 
Buchu, 546 

Buckthorn, 507 

Burgund] pitch, 610 

pitch plaster, 810 
Burnt alum, tilt; 

Cabinet baths, (nun 
Cacao but ter, 787 

( acodylic acid, 359 
Caffeina, 209 

citrata, 209 

citrate effervescens, 
209 
Caffeine, 209 

and sodium benzoate, 

217 
poisoning, 217 
Calabar bean, 1 15 
Calabarine, 146 
Calcii bromidum, 15 1 
Calcii carbonas pra'cipi- 
tat US, 636 

chloridum, 636 

hypophosphis, 336 
phosphas prscipita- 

tUS, 334 
sulphas exsiccat us, 
636 

Calcium, 635 

bromide, 154 
carbonate, 635 
chloride, 635, 637 
hypophosphite, 336 
lactophosphate, 336 
oxide, 635 
phosphate, 335 
sulphate, 635 
sulphide, 694 

California buckthorn, 507 

Calisaya officinalis, 419 

Calmatives, 14 

Calomel, 360, 513 

Calumba, 477 

Calx, 636 

chlorinata, 656 
sulphurata, 694 

Cambogia, 519 

Campherol, (note) 187 

Camphor, 187 

artificial, 548 
bromated, 161 
cymol, (note) 1S7 
liniment, 187 
-menthol, (note) 852 
mixture, Hope's, 332 
monobromated, 161, 

L87 
poisoning, KM 
water, 187 



762 



GENERAL INDEX 



Camphora, 187 

monobromata, 161, 
187 
Camphorated tincture of 

opium, 58 
Camphoric acid, 192 
Canada balsam, 548 

fleabane, 555 

turpentine, 548 
Canadian hemp, 236 
Canadine, 592 
Cane sugar, 544 
Cannabene, 114 

tannate, 117 
Cannabin, 114 
Cannabinol, 114 
Cannabinon, 114 
Cannabis indica, 113 

sativa, 113 
Canquoin's paste, 614 
Cantharidal collodion, 605 
Cantharides, 604 

cerate, 605 

poisoning, 605 

plaster, 605 
Cantharidin, 604 

salts, (note) 605 
Cantharis, 604 

vesicatoria, 604 
Cape aloes, 504 
Capsicin, (note) 483 
Capsicum, 483 

annuum, 483 

as counter-irritant, 
608 

fastigiatum, 483 
Carbamic ether, 89 
Carbazotic acid, 647 
Carbo animalis, 652 

purificatus, 652 

ligni, 652 
Carbolated vaseline, 664 
Carbolic acid, 664 

poisoning, 670 
Carbon bisulphide, 610 

compounds, 663 
Carbonei disulphidum,610 
Carbonic quinic ester, 436 
Cardamom, 482 
Cardiac depressants, 256 

massage, 46 

stimulants, 182 
Cardiants, 182 
Carica papaya, 651 
Carlsbad salts, (note) 508 
Carminatives, 478 
Carolina jessamine, 172 
Carrageen, 618 
Carrageenin, 618 
Carron oil, 636 
Carthagena ipecacuanha, 

488 
Caryophyllus, 481 
Cascara sagrada, 507 
Cascarin, 507 
Cassia acutifolia, 505 



Cassia angustifolia, 505 

bark, 481 

fistula, 503 
Castile soap, 600 
Castor oil, 521 

oil beans, 521 
Cataplasm of kaolin, 628 
Cataplasma kaolini, 628 
Cathartic acid, 506 
Cathartic oils, 520 
Cathartics, 497 
Caustic potash, 535 

soda, 632 
Cayenne pepper, 483 
Centric emetics, 488 

local anaesthesia, 54 
Cephaeline, 488 
Cephaelis acuminata, 488 

ipecacuanha, 488 
Cera alba, 622 

flava, 622 
Cerasus serotina, 477 
Cerata, 3 
Cerates, 3 

Cerate of camphor, 187 
Ceratum, 622 

camphorae, 187 

plumbi subacetatis, 
293 

resinse, 548 

compositus, 548 

cantharidis, 548, 605 
Cerii oxalas 307 
Cerium oxalate, 307 
Cetaceum, 622 
Cetraria, 620 

islandica, 620 
Cetraric acid, 620 
Cetrarin, 620 
Ceylon cinnamon, 481 
Chalk, 636 

mixture, 636 
Chamomile, 483 
Champagne, 207 
Charcoal, 652 
Charta arsenicalis com- 
posita, (note) 572 

sinapis, 607 
Chenopodium, anthelmin- 

ticum, 643 
Children, comparative 

dose for, 7 
Chillies, 483 
Chimaphila, 547 

umbellata, 547 
Chimaphilin, 547 
Chinese cinnamon, 481 
Chirata, 477 
Chloral, 75 

hydrate, 75 

poisoning, 81 

poisoning, chronic, 
82 
Chloralamid, 89 
Chloralformamid, 89 
Chloralformamidum, 89 



Chloralose, 91 
Chloralum hydratum, 76 
Chloretone, 91 
Chloric ether, 449 
Chloride of lime, 656 
Chlorinated lime, 656 
Chlorine, 656 

water, 657 
Chloroform, 30 

liniment, 30 

water, 30 
Chloroformum, 30 
Chlorum, 656 
Choke cherry, 477 
Cholera antitoxin, 411 
Choline, 399 
Chondodendron tornento- 

sum, 547 
Chondrus, 618 

crispus, 618 
Chromic acid, 615 
Chromii trioxidum, 615 
Chromium trioxide, 615 
Chronic antimony-poison- 
ing, 262 

arsenic-poisoning, 356 

chloral-poisoning, 82 

digitalis-poisoning, 
233 

lead-poisoning, 295 

sulphonal-poisoning, 
85 
Chrysaroba, 600 
Chrysarobin, 600 
Chrysarobinum, 600 
Chrysophan, 504 
Chrysophanic acid, 503 
Churrus, 113 
Cigarettes, arsenical, 

(note) 572 
Cimicifuga, 18 

racemosa, 18 
Cinchona, 419 

ledgeriana, 419 

succiruba, 419 

rubra, 419 
Cinchonidinae sulphas, 420 
Cinchonidine, 419 

sulphate, 420, 435 
Cinchoninae sulphas, 420 
Cinchonine, 435 

sulphate, 435 
Cinchonism, 433 
Cineol, 440 
Cinnaldehydum, 481 
Cinnamic acid, 693 

aldehyde, 481 
Cinnamomum, 481 

camphora, 187 

zeylanicum, 481 
Cinnamon, 481 

water, 480 
Citrated caffeine, 209 
Citric acid, 512 
Citrine ointment, 371 
Citrullus colocynthis, 516 



(1KNKRAL IN HI \ 






Clarke's Rule for Doses, 

(note) 7 
Classification, 1 1 
Claviceps purpurea, .Ys 2 
Clay, 627 
Clove tea, 181 
Cloves, im 
Coca, 117 
Cocaina, l is 
Cocaine hydrochloridum, 

lis 
Cocaine, 1 18 

habit, 128 

hydrochloride, 1 is 

poisoning, 127 
Cocainismus, 128 
Coca-tannic acid, 118 
Cocoa-butter, 622 
Codeina, 58 
Codeine phosphas, 58 

sulphas, 58 
Codeine, 58, 72 

phosphate, 58 

sulphate, 58 
Cod-liver oil, 3S7 
Coffea arabica, 209 
Coffee, 209 

Colchiceine, (note) 391 
Colchicina, 391 
Colchicine, 391 
Colclucum, 390 

autuinnale, 390 

conn, 390 

poisoning, 394 

seed, 393 
Cold, as an antiseptic, (5,53 

cream, 622 
Colica pictonum, 296 
Collargol, 320 
Collodion, (530 
Collodium, 630 

cantharidatum, 605, 
630 

flexile, 630 

stvpticum, 285, 630 
Colloidal silver, 320 
Colocynth, 516 
Colocynthin, 516 
Colocynthis, 516 
Columbian spirits, 208 
Columbin, 477 
Columbo, 477 
Commercial calcium sul- 
phide, 694 

zinc oxide, 308 
Comparative power of dis- 
infectants, 703 
Compound arsenical pa- 
per, (note) 572 

cathartic pills, 517 

decoction of sarsapa- 
rilla, 397 

effervescing powder, 
508 

extract of colocvnth, 
517 



Compound fluid extract of 

sar-apaiilla, :> l .>7 

infusion of senna, 
506 

jalap powder, 516 

laxal ive pills. 505 

licorice powder, ,">ut'. 
mixture of iron, 324 
mixture of licorice, 
til '.i 

pills of rhubarb, 50 1 
powder of chalk, 636 

powder of jalap, oil! 
powder of morphine, 

68 
powder of rhubarb, 

50 1 
resin cerate, 5 18 

solution of chlorine, 

657 
solution of crcsol, 

678 
solution of iodine, 

374 
solution of sodium 

phosphate, .508 
spirit of ether, 26 
spirit of juniper, 554 
syrup of hypophos- 

phitcs, 336 
syrup of sarsaparilla, 

397 
syrup of squill, 528 
tincture of benzoin, 

691 
tincture of carda- 
mom, 480 
tincture of cinchona, 

419 
tincture of gambir, 

288 
tincture of gentian, 

623 
tincture of lavender, 
480 
Confectio rosa?, 289 

senna?, 506 
Confection of rose, 289 

of senna, 506 
Confectiones, 3 
Confections, 3 
Coniine, 176 

hydrobromide, 176 
Coniuni, 175 

maculatum, 175 
poisoning, 178 
Convallamarin, 246 
Convallaria, 246 
majalis, 246 
Convallarin, 246 
( lonvolvulin, 516, 517 
Convolvulus scammonia, 

517 
Copaiba, 552 

langsdorffii, 552 
-red, 553 



Copaivio acid. 
Copper, 309 

ining, ■in 
sulphatt 

Copperas, I 

Cornutine, 582 
Corrosive mercuric chlo- 
ride, 360 

sublimate, 360 

as a caustic, 61 I 

as a disinfectant, 
654 

poisoning, 371 
Corsican moss, 620 
Corynanthe yohimbi, 556 
Cosmoline, 623 
Cotarnine gauze, 291 

hydroohlorate, 291 
Cotton-root, 598 

-seed oil, 622 
Couch-grass, 548 
Counter-irritants, 601 
Countess powder, 419 
Coxe's hive syrup, 528 
Cracked wheat, 502 
Cramp-root, 581 
Cranesbill, 289 

Cream of tartar, 508 

( Ireasote, (57 1 
Creolin, 679 

otal, 674 
Creosote, 674 

carbonate, 674 

water, 674 
Creosotum, 674 
Cresol, 678 
Cresylic acid, 678 
Cresylol, 678 
Creta prajparata, 636 
Croton oil, 522 

tigtium, 522 
Crotonoleic acid, 522 
Croton-resin, 522 
Crude camphor, 187 
Cryptopine, 72 
Crystallized digitalin, 218 
Cubeb, 553 
Cubeba, 553 
Cubebic acid, 553 
Cubebin, 553 
Cucurbita pepo, 645 
Cupri sulphas, 310 
Cuprum, 309 
Cusso, 645 

Cyanogen gas, (note) 275 
Cyanohemoglobin, 278 
Cynips tinctori, 288 
Cypnpedin, 19 
Cypripedium, 19 

hirsuturn, 19 

parviflorum, 19 
Cystogen, 556 
( Yt isine, 609 
Cytisus laburnum, 609 
i rius, 2 Is. 5'_';i 



764 



GENERAL INDEX 



Dandelion, 397 

Daphne mezereum, 397 

Daphnin, 397 

Datura stramonium, 94 

Daturine, 94 

Deadly night-shade, 94 

Decocta, 2 

Decoction of kava, 556 
of sarsaparilla, com- 
pound, 397 

Decoctions, 2 

Delirifacients, 94 

Demulcents, 617 

Deodorized opium, 58 
tincture of opium, 58 

Depresso-motors, 145 

Diethylsulfondimethyl- 
methan, 83 

Diaphoretics, 559 

Diastase, 650 

Dibasic phosphoric acid, 
334 

Diethylendiamine, 543 

Diethylmalonyl urea, 91 

Di-fluor-diphenyl, 659 

Digestants, 648 

Digitalein, 218 

Digitalin, 218 

crystallized, 218 
German, 218 
of Kiliani, 218 

Digitalinum Germani- 
cum, 218 
verum, 218 

Digitalis, 218 

eriostachys, (note) 

218 
ferruginea, (note) 218 
fontanesii, (note) 218 
gigantea, (note) 218 
glandulosa,(note) 218 
nervosa, (note) 218 
poisoning by, 232 
purpurea, 218 

Digitonin, 218 

Digitoxin, 218 

Dihydroxyl-quinine, 
(note) 421 

Dii odopa raphe nolsul- 
phonic acid, 387 

Di-isobutyl-ortho-cresol- 
iodide, 387 

Diluted acetic acid, 290 
alcohol, 192 
hydriodic acid, 374 
hydrobromic acid, 

154 
hydrochloric acid, 

331 
hydrocyanic acid, 276 
mercurial ointment, 

360 
nitric acid, 331 
nitro -hydrochloric 

acid, 333 
phosphoric acid, 334 



Diluted prussic acid, 276 
silver nitrate, 438 
solution of lead sub- 
acetate, 293 
sulphuric acid, 330 
Dimethylamidophenyl- 
dimethylpyrazolon, 472 
Dimethylarsenic acid, 359 
Dimethylxanthin, 531 
Dionine, 73 
Dioxypurin, 531 
Dioxybenzene, 683 
Dioxymethyl-anthra- 

quinone, 503 
Diphtheria antitoxin, 408 
Disinfectants, 653 

comparative power 

of, 703 
proprietary, (note) 
658 
Disodium hydrogen phos- 
phate, 511 
Di-stearyl-glycerophos- 

phate of cholin, 399 
Disulphones, 83 
Dithymol-diiodide, 386 
Diuretics, 525 
Diuretin, 531 
Dogbane, 236 
Donovan's solution, 346, 

371 
Dormiol, 90 
Doses, rules for, 6 
Dover's powder, 58 
Drastic cathartics, 515 
Dried alum, 292 

calcium sulphate, 636 
ferrous sulphate, 449 
sodium arsenate, 346 
sodium carbonate, 

801 
suprarenals, 323 
thyroid body, 406 
Dry heat as a germicide, 

653 
Dryobalanops camphora, 

(note) 187 
Dryopteros filix mas, 643 

marginale, 644 
Dunbar's hay-fever anti- 
toxin, 411 
Duotal, 677 

Ecballium elaterium, 518 
Ecgonine, 119 
Effervescent citrated caf- 
feine, 209 

lithium citrate, 542 
magnesium sulphate, 

508 
sodium phosphate, 
508 
Eggnog, 207 
Elaterin, 519 
Elaterinum, 519 
Elaterium, 518 



Elettaria repens, 482 
Elixir adjuvans, 480, 619 
aromaticum, 480 
ferri, quininae et 
strychninae phos- 
phatis, 324 
of iron quinine and 
strychnine, 324 
Elm bark, 618 
Emetics, 485 
Emetine, 488, 493 
Emmenagogues, 579 
Emodin, 503 
Emollients, 621 
Emplastra, 3 

Emplastrum belladonnas 
95 

hydrargyri, 361 
plumbi, 293 
saponis, 293 
Empyreumatic oils, 61 
Emulsa, 2 
Emulsin, 478 
Emulsion of ammoniac, 
577 

• of asafetida, 16 
of chloroform, 30 
of cod-liver oil, 388 
of cod-liver oil with 
hypophosphites, 
388 
of oil of turpentine, 
548 
Emulsions, 2 

PZmulsum ammoniaci, 577 
asafcetidae, 16 
chloroformi, 30 
olei morrhuae, 388 
cum hypophosphi- 
tum, 388 
terebinthinae, 548 
Encephalopathia satur- 

nina, 297 
Endermic administration, 

5 
Enemata, 500 
Eosote, 847 
Epinephrin, 242 
Epispastics, 604 
Epsom salt, 508 
Ergot, 582 
Ergota, 582 
Ergotin, 583 
Ergotinin, 583 
Ergotism, 590 
Ergotoxin, 583 
Erigeron canadense, 555 
Erythrol tetranitrate, 

170 
Erythroxylon coca, 117 

truxillense, 117 
Escharotics, 611 
Eserine, 145 

salicylate, 146 
Essence of ginger, 482 
of peppermint, 480 



GENERAL INDEX 






Essence of spearmint . 180 
Essential salts of lemons. 

685 
Ether, 26 

Bertoni's. (note) 161 

pneumoma, (.nolo) 39 
Ethereal oil, (note) 26 
Ethyl alcohol, 192 

acetate, 19 
Kthyl bromide, 36 

carbamate, 89 

chloride, 35 

nitrite, 161 

oxide, 26 
Ethylaoetamidophenol, 

(note) 466 
Bthylcarbonic ester of 

quinine, 436 
Ethylene bromide, 36 
Ethylsulphonic acid, 83 
Ehicaine, 51 

Eucalypsinthe, (note) 440 
Eucalyptol, 410 
Eucalyptus, 430 

globulus, 430 

gum, 1 10 
Eugenia aromaticus, 4S1 

jambolana, 398 
Eugenol, 480, 690 
Euonymin, 520 
Euonymus, 520 

atropurpureus, 520 
Euquinine, 436 
Excito-motors, 131 
Exogoniuin purga, 516 
Expectorants, 570 
Expressed oil of almonds, 

622 
1 "xi tact of aconite, 385 

of aloes, 505 

of belladonna leaves, 
95 

of Calabar bean, 146 

of cannabis indica, 
114 

of cascara sagrada, 
507 

of cimicifuga, 18 

of colchicum root , 
391 

of colocynth, 517 

of conium, 176 

of dandelion, 397 

of digitalis, 218 

of ergot, 583 

of euonymus, 520 

of gentian, 477 

of glycyrrhiza, 619 

of hsematoxylon, 288 

of hemp, 114 

of hyoscyamus, 95 

of Indian cannabis, 
114 

of krameria, 288 

of licorice, 619 

of logwood, 288 



Extract Of mall , (').".() 

of mix vomica, 131 

of opium, 68 

of physostigma, i 16 

of quassia, 476 

of rhatanv, 288 

of rhubarb, 50 i 

of scopola, 95 

of stramonium, 95 

of sumbul, 17 

of taraxacum, 397 

of wahoo, .")'_'() 

Extracta, 3 
Extracts, fluid, 3 

solid, 3 
Extract urn aloes, 505 

belladonnas foliorum, 
95 

cannabis indica', 1 11 
cimicifuga', 18 

colchici cormus, 391 
colooynthidis. 517 
colocynl hidis com- 
positum, 517 

digitalis, 218 
ergots, 583 
euonymus, 520 
gentians, 477 

glycyrrhiza-, til!) 

purum, tilli 
haunatoxyli, 288 

hyoscyami, 95 

krameria), 288 

malti, 650 
Ducis vomica), l ."> 1 
opii, 58 

physostigmat is, l i<> 
quassise, 176 
rhamm purshianse, 

507 
rhei, 504 
scopohc, 95 
stramonii, 95 
sumbul, 17 
taraxaci, 397 
Extraneous remedies, 631 

Fagus sylvatica, 674 
Fel bovis purificatum, 508 
Fennel water, 480 
Ferratin, 327 
Ferri carbonas sacchar- 
atus, 323 

chloridum, 323 

citras, 323 

et ammonii citras, 

323 
et ammonii sulphas, 

323 
et ammonii tartras, 

323 
et potassii tartras, 

323 
et quininae citras, 323 
et quinina> citras solit- 
bilis, 323 



Ferri el strychnina < 
323 
hydroxidum, 323 
hydroxidum cum 
magnesii oxido, 
, 328 
hypophosphiB, 323, 

phosphas solubilis, 
323 

pyrophosphas solu- 
bilis, 323 

sulphas, 823 
sulphas eZSioOal lis, 
323 

sulphas granulate , 

323 

Ferric ammonium sul- 
phate, 323 
chloride, 323 
citrate, 323 

hydroxide 323, 328 
hydroxide with mag* 
Desia, 323 

hvpophosphilc, 323, 

:;;;i; 
phosphate, soluble, 

323 
pyrophosphate, solu- 
' ble, 323 
Bubsulphate, soluf ion 

of 323 

Bulphate, solution of, 
323 

FerrOUS carbonate, sac- 

charated, 323 

sulphate, 323, 656 
sulphate, dried, 323 

Ferrum, 323 

reductum, 323 

Ferula fcetida, 16 
sumbul, 17 

Ficus, 503 

Figs, 503 

Filicic acid, 644 

Filix mas, 643 

Fire, 653 

Flake manna, 503 

Flaxseed, 619 
poultice, 628 
tea (infusion), 619 

Fleabane, 555 

Flexible collodion, 630 

Fluidextract of aconite, 
267 

of apocynum, 236 

of barberry, 477 

of belladonna root , 

95 
of bitter orange peel, 

480 
of black haw, 581 
of buchu, 546 
of ealumba, 477 
of cannabis indica, 
114 



7G6 



GENERAL INDEX 



Fluidextract of capsicum, 
483 

of cascara sagrada, 

507 
of chimaphila, 54S 
of chirata, 477 
of cimicifuga, 18 
of cinchona, 419 
of coca, 118 
of colchicum seeds, 

391 
of conium, 176 
of convallaria, 246 
of couch-grass, 548 
of cramp-root, 581 
of cubeb, 553 
of cypripedium, 19 
of dandelion, 530 
of digitalis, 218 
of ergot, 583 
of eucalyptus, 440 
of euonymus, 520 
of frangula, 507 
of gelsemium, 172 
of gentian, 477 
of geranium, 289 
of ginger, 482 
of glycyrrhiza, 619 
of grindelia, 576 
of guarana, 209 
of hamamelis, 289 
of hemp, 114 
of hydrastis, 592 
of hyoscyamus, 95 
of Indian cannabis, 

114 
of ipecacuanha, 4S9 
of jaborandi, 563 
of kava, 556 
of krameria, 288 
of leptandra, 520 
of licorice, 619 
of lobelia, 171 
of lupulin, 18 
of matico, 554 
of mezereon, 397 
of nux vomica, 131 
of oak bark, 289 
of pareira brava, 547 
of pilocarpus, 563 
of pomegranate, 646 
of podophyllum, 518 
of quassia, 476 
of quillaja, 574 
of rhamnus purshi- 

ana, 507 
of rhatany, 288 
of rhubarb, 504 
of rhus glabra, 288 
of rose, 289 
of sanguinaria, 577 
of sarsaparilla, 397 
of savine, 579 
of scopola, 95 
of senega, 574 
of senna, 506 



Fluidextract of serpenta- 
ria, 484 

of spigelia, 643 

of squill, 528 

of stillingia, 397 

of stramonium, 95 

of sumach, 288 

of sumbul, 17 

of taraxacum, 397 

of triticum, 548 

of uva ursi, 546 

of valerian, 15 

of veratrum, 263 

of wild cherry, 478 

of witch hazel, 289] 

of xanthoxylum, 398 
Fluidextracta, 3 
Fluidextracts, 3 
Fluidextractum aconiti, 
267 

apocyni, 236 

aromaticum, 480 

aurantii amari, 430 

belladonna? radicis, 
95 

berberidis, 477 

buchu, 546 

calumbae, 477 

cannabis indicse, 114 

capsici, 483 

chimaphila?, 548 

chiratae, 477 

cimicifugae, 18 

cinchonse, 419 

coca?, 118 

colchici seminis, 391 

conii, 176 

convallaria?, 246 

cubeba?, 553 

cypripedii, 19 

digitalis, 218 

ergotae, 583 

eucalypti, 440 

euonymi, 520 

frangula?, 507 

gelsemii, 172 

gentianse, 477 

geranii, 289 

glycyrrhizae, 619 

granati, 646 

grindeliae, 576 

guarana?, 209 

hamamelidis folio- 
rum, 289 

hydrastis, 592 

hyoscyami, 95 

ipecacuanha?, 489 

krameria?, 288 

leptandra?, 520 

lobelia?, 171 

lupulini, 18 

matico, 554 

mezerei, 397 

nucis vomica?, 131 

pareira?, 547 

pilocarpi, 563 



Fluidextractum podo- 
phylli, 518 

pruni Virginiana?, 47S 

quassia?, 476 

quercus, 289 

quillaja?, 574 

rharnni purshianae, 
507 

aromaticum, 507 

rhei, 504 

rhois glabra?, 288 

rosa?, 289 

sabina?, 579 

sanguinaria?, 577 

sarsaparillae, 397 

compositum, 397 

scilla?, 528 

scopola?, 95 

senega?, 574 

senna?, 506 

serpentaria?, 484 

spigelia?, 643 

stillingia?, 397 

stramonii, 95 

sumbul, 17 

taraxaci, 397 

tritici, 548 

uva ursi, 547 

Valeriana?, 15 

veratri, 263 

viburni opuli, 581 

viburni prunifolii,581 

xanthoxyli, 398 

zingiberis, 482 
Fluorides, 659 
Fluoroform, 659 
Fluoroformol, 659 
Fluorol, 659 

Foods, artificially diges- 
ted, 649 
Formaldehyde, 686 
Formalin, 686 
Formin, 556 
Formol, 686 
Formyl,686 

bromide, 160 
Fowler's solution, 346 
Foxglove, 218 
Frangula, 507 
Frangulin, 507 
Fraxinus ornus, 503 
French digitalin, 218 
French weights and meas- 
ures, 706 
Fuller's earth, 627 
Fumigations, mercurial, 

370 
Fused silver nitrate, 313 

Gaduin, 388 

Gadus morrhua, 387 

Galla, 287 

Gallic acid, 287 

Gallo-tannic acid, 284 

Galls, 287 

Gambir, 2S8 



GENER \l. 1M»I \ 



767 



Gamboge, 519 

in sori.s, 520 
Gangrenous ergotism, 500 
Garoinia hanburii, 519 
Gaultheria, oil of, i ii> 
Gelatin, 400 

tannate, 289 
Gelatinum, 100 

glyeennatum, 102 
Gelatoae Bilver, 319 
Gebemine, 172 
t ielseminin, 172 
I icNemium. 172 

pAJanning 17 | 

sempervirens, 172 
General remedies, 1 1 

Gentian, I7t; 
Gentiana, t7t> 

tutea, 470 
Gentiopikrin, 177 
Gentimo acid, iT»> 
Geranium. 289 

maeulatum, 289 
German chamomile, 484 

digitalin, 218 
Germicides, 653 
Gigartina mamilloBa, 618 
Gin, 555 
Ginger, 482 

Glacial acetic acid, 200 
Glandule Buprarenales, 
sicca*, 242 

thyroidea sices, 406 
Glauber salt, 508 
Glucosides, 2 
Glycerine, 624 

salicylate, 456 
Glyoerinated gelatin, 402 
Glycerinum, 624 
Cilycerita, 3 

Glycerite of boroglycerin, 
695 

of hydrastis, 502 

of phenol, 664 

of starch, 622 

of tannin, 285 
Glycerites, 3 

Glvceritum acidi tannici, 
285 

amyli, 622 

boroglycerini, 695 

hydrastis, 592 

pnenolis, 664 
Glycerol, 624 
Glvcero-phosphoric acid, 

337 
(dyceryl trinitrate, 161 
Gly co-formalin, 689 
Glycosal, 456 
' ilveyrrhiza, 619 

glabra, 619 

glandulifera, 619 
GlycyrThizin, 619 
Glycyrrhizinum ammoni- 

atum, 619 
Goa powder, 600 



Gold and sodimn ohloride, 
372 

< lold iodide, 373 

oxide, 373 
Golden seal, 692 
I tassypii cortex, 598 
Gossypium herbaoeum, 
598 

purificatum, 598 
Goulard's extract, 293 
( Iranatum. 6 16 
( Iray powder, : i t v« » 
( Ireen ginger, 482 

soap, 600 
Griffith^ mixture, 324 
Grindelia, 576 

robusta, 576 

Bquarrosa, 576 
Guaiac, 397 

resin, 397 
Guaiacol, 676 

carbonate, t>77 
Guaiacolis carbonas, 677 
Guaiaconic acid, 502 
Guarana, 209 
Guaranine, 209 
Gum arabic, 617 
Gun-cotton, 630 
Gunjah, 113 
Gutta-percha, 630 

Bsmatoporpbyrin, 86 

I hematoxylin, '2SS 
FLematoxylon, 288 

campechianum, 2SS 
Hagenia abyssinica, 645 
Halogen disinfectants, 656 
Hamanielis, 289 

virginica, 289 
Hashish, 113 

Hay-fever antitoxin, 411 
Heat as a disinfectant, 

653 
Heavy magnesia, 634 

oil of wine, (note) 26 
Hedeoma pulegioides, 580 
Hedonal, 90 
Hemp, 113 
Henbane, 95 
Heroine, 74 
Heteroxanthin, 531 
Hetol, 693 

Hexamethylenamina, 556 
Hexamethylenetetramine, 

556 
High enemata, 500 
Hippurate of lime and 

lithia, (note) 691 
Hippuric acid, 691 
Hive syrup, Coxe's, 528 
Hoffmann's anodyne, 26 
Holly tea, 209 
Homatropinre hydrobro- 

midum, 112 
Homatropine, 1 1 2 

hydrobromide, 112 



Honey of i 

Hopes camphor mix) lire, 
332 

Hops, 17 

Hordeum, 620 
Horehound, 677 
I lot baths, 569 
Huanuco coca, 1 17 

Humulus, 17 

lupulus. 17 
Huxham's tincture, 1 19 
Hydragogue diuretics, 628 
Hydrargyri ohloridum 
corrosivum, 360 
chloridum mite, ;;.'><' 
iodidum, (lavum, 360 
rubrum, 360 

oxidum llavum, 360 

rubrum, 360 

Hydrargyrum, 360 

ammoniatum, 360 

cum creta, 360 
Hydrastin, 592 
Hydrast ina, 592 

Hydrastine, 502 
HydrastininsB hydrochlo- 

ras, 596 
Hydrast ininc hydroehlo- 

rate, 596 
Hydrastis, 592 

canadensis, ",02 
Hydrated chloral, 75 
Hvdrated oxide of iron, 

328 
Hydriodic acid, 374 
Hydrobromic acid, 153 
Hydrochinone, (note' 517 
Hydrochloric acid, 331 

poisoning, 320 
Hydrocyanic acid, 275 

poisoning by, 280 
Hydrofluoric acid, 650 
Hydrogen dioxide, solu- 
tion of, 661 

peroxide, solution of, 

661 
sulphide, 51 8 
Hydroquinone, 683 
Hydrous wool-fat, 623 
Hydroxybenzene, 664 
Hyoscinae hydrobromi- 

dum, 100 
Hyoscine, 108 

hydrobromide, 100 
poisoning, 1 12 
Hyoscyamins hydrobro- 
midum, 95 
sulphas, 05 
Hyoscyamine, 94 

hydrobromide, 95 
sulphate, 95 
Hyoscyamus, 95 

niger, 95 
Hypercme 
Hypochlorites, 824 
Hypodermic injections, I 



768 



GENERAL INDEX 



Hypodermic purgation, 

501 
Hypodermoclysis, 526 
Hypophosphites, 336 
Hypophosphorous acid, 

336 
Hypophysis, 406 
Hypoquebrachine, 179 

Iceland moss, 620 
Ichthalbin, 396 
Ichthargan, 320 
Ichthyodin, 396 
Ichthyol, 395 

albuminate, 396 
Idiosyncrasies, 6 
Igasuric acid, 131 
Ignis sacer, 590 

sancti Antonii, 590 
Ilex cassine, 209 

paraguaiensis, 209 
Incompatibilities, 10 
Index of diseases, 710 
Indian cannabis, 113 

corn, 619 

hemp, 113 

meal, 502 
Indications for drugs, 3 
Inee poison, 237 
Infiltration-anaesthesia, 

52 
Infusa, 2 
Infusion of cloves, 481 

of digitalis, 218 

of senna, compound, 
506 

of wild cherry, 478 
Infusions, 2 
Infusum digitalis, 218 

pruni virginianae, 478 

senna? compositum, 
506 
Injections, 5 

subcutaneous, 4 
Insoluble gold prepara- 
tions, 373 
Intravenous salt solution 
in poisoning, (note) 127 
Inunctions, mercurial, 

369 
Iodine, 373 

as a disinfectant, 657 

poisoning, 378 
Iodipin, 380 
Iodism, 379 
Iodoform, 380 

poisoning, 384 
Iodoformogen, 387 
Iodoformum, 381 
Iodol, 386 
Iodolum, 386 
Iodothyrin, 403 
Iodum, 374 
Ions, theory of, 533 
Ipecacuanha, 488 

as a diaphoretic, 502 



Ipecacuanha as an expec- 
torant, 573 
Ipccacuanhic acid, 489 
Irish moss, 618 
Iron, 323 

and ammonium, cit- 
rate, 323 
and ammonium tar- 
trate, 323 
and potassium tar- 
trate, 323 
and quinine citrate, 

323 
and strychnine cit- 
rate, 323 
cacodylate, 359 
citrate, 323 
tartrates, 323 
wire, 323 
Irritants, 600 

and counter-irritants, 
600 
Isaconitine, 267 
Isarol, 396 
Iso-butyl nitrite, (note) 

161 
Isopelletierine, 646 
Isophysostigmine, 146 
Isopilocarpine, (note) 

563 
Isopral, 90 
Isopunicine, 646 
Itrol, 319 

Jaborandi, 562 
Jaborine, (note) 563 
Jacket-poultice, 629 
Jaguarandy, 562 
Jalap, 516 
Jalapa, 516 
Jalapin, 517 
Jamaica ginger, 482 
Jamaica quassia, 476 
Jambul, 398 
Jamestown weed, 94 
Jamguarandi, 562 
Japaconitine, (note) 266 
Japanese belladonna, 95 
Jateorhiza palmata, 477 
Jerusalem oak, 643 
Jervine, 262 
Jessamine, 172 
Juniper, 554 
Juniperus, 554 

communis, 554 

sabina, 579 

Kamala, 647 
Kaolin, 627 
Kava, 555 
Kava-kava, 555 
Kava resin, 555 
Kavin, 555 
Kawa, 555 

Kiliani's digitalin, 218 
Kino, 288 



Kino-tannic acid, 284 
Kola nut, 209 
Kombe 1 poison, 237 
Kosin, 645 
Kosotoxin, 645 
Kousso, 645 
Krameria, 288 

ixina, 288 

triandra, 288 
Kuzazu, (note) 266 

Labarraque's solution, 656 
Lactic acid, 616 
Lactophosphate of lime, 

335 
Lactuca virosa, 19 
Lactucarium, 19 
Lactucin, 19 
Lady Webster pills, . r )(). r ) 
Lanolin, 622 
Lard, 622 

Large enemata, .500 
Largin, 319 
Laudanine, 72 
Laudanum, 58 
Lavage of the blood, 

(note) 127 
Lavandula spica, (note) 

475 
Lavender, oil of, 480 
Laxative foods, 502 
Laxatives, 497 
Lead, 293 

acetate, 293 

carbonate, 293 

chromate, (note) 296 

colic, 296 

iodide, 293 

nitrate, 293, 656 

oxide, 293 

plaster, 293 

poisoning, 294 

water, 293 
Lecithin, 399 
Ledoyen's disinfectant 

solution, 294, 656 
Lemon-juice, 512 
Lemon-peel, 480 
Lemons, essential salt of, 

685 
Leptandra, 520 
Leptandrin, 520 
Levant wormseed, 639 
Lichen starch, 620 
Lichenin, 620 
Licorice, 619 

root, 619 
Light magnesia, 634 
Lily of the valley, 246 
Lime, 635 

juice, 512 

liniment, 636 

unslaked, 636 

water, 636 
Limonis cortex, 480 

succus, 480, 512 



GENERAL INDEX 



-f.!l 



Liniment of ammonia, 183 
>>i belladonna, 96 
of camphor, 1 87 
of chloroform, 30 
of lime, 636 
of soap, 1st 
of i urpenl ine, 5 I s 

Liniment 

Liniments, 3 

Liniment mn ammonite, 

is:: 

belladonna, 95 
calcis. 636 
camphors, 187 
cbloroformi, 30 
saponis, L87 
terebinthine, 5 is 

Linseed oil, 622 
Linuin, 019 

usitatissimum, 619 
Liquefied phenol, 664 
Liquid petrolatum, 022 
Liquor acidi arsenosi, 
340 

arseni et hydrargyri 

iodidi, 340 
calcis, 030 

chlori compositus, 656 
cresolis compositus, 

078 
ferri ohloridi, 324 
ferri et ammonii ace- 

tas, 324 
ferri subsulphatis, 

32 t 
ferri tersulphatis, 324 
formaldehydi, 080 
gutta-percha 1 , 030 
hydrargyri nitratis, 

61 l 
iodi compositus, 37 I 
magnesii citratis, 508, 

512 
plumbi subacetatis, 

293 
plumbi subacetatis 

dilutus, 293 
potassse, 535 
potassii arsenitis, 340 
potassii citratis, 512, 

535 
potassii hydroxide, 

535 
sodse chlorinata?, 050 
sodii arsenatis, 340 
sodii hydroxidi, 032 
sodii phosphatis com- 
positus, .508 
zinci chloridi, 308 
Liquores, 2 
Listerine, 703 
Litharge, 293 
Lithii benzoas, 542 
bromidum, 154 
carbonas, 542 
citras, 542 
49 



Lithii citras effervescens, 

512 
salicj las, 1 16 
Lithium, 542 

arsenical solution of, 

543 

benzoate, ■"> 12 
bromide, 154 
carbonate, 5 12 
citrate, 5 12 
mercuric iodide, 655 

salicylate, 440 
Lobelia, 170 

inflata, 170 
Lobeline, 170 

Local ana-sthesia, 51 

applications, 5 

remedies, 475 
Logwood, 288 
Lozenges, 3 
Lngol's solution, 374 
Lunar caustic, 313 
Lupulin, 17 
Lupulinum, 17 
Lycoctonine, (note) 200 

Mace, 481 
Magnesia, 034 
Magnesii carbonas, 035 
oxidum, 035 
oxidum pondcrosum, 

035 
sulphas, 508 
sulphas effervescens, 
508 
Magnesium carbonate, 035 
oxide, 035 
sulphate, 510 
Male fern, 043 
Mallotus philippinensis, 

047 
Mali, 050 
Manganese, 328 
dioxide, 328 
sulphate, 328 
Mangani dioxiduni praj- 
cipitatum, 329 

hypophosphis, 32!) 
sulphas, 329 
Manna, 503 
Mannite, 503 
Marble, 035 
Marjoram, oil of, (note) 

475 
Marrubiin, 577 
Marrubium, 577 
Martineau's solution, 

(note) 543 
Mass of ferrous carbonate, 
323 

of mercury, 300 
Massa ferri carbonatis, 
323 

hydrargyri, 300 
Massage of the heart, 40 
Mate:, 209 



Materia medica, l 
Maticin, 551 
Matico, 554 
Matricaria, is I 

chamomilla, is i 
May-apple, 517 

Meadow saffron, 390 
Measures of the metrical 

system, 700 
Mechanical emetics, 490 
Meconic acid, 57 
Meconine, 57 
Medulla sassafras, 619 
Mel rosea, 289 
Melaleuca leucadcndrou, 

440 
Melia azedarach, 047 
Mentha piperita, 480 
pulegium, 580 
viridis, 480 
Menthol, 480, 081 
Mercurial cachexia, 305 
fumigations, 370 
inunctions, 309 
ointment, 300 
pills, 301 
plaster, 301 
poisoning, local, 305 
ptyalism, 302 
purgatives, 513 
Mercuric nitrate, solution 
of, 014 

cliloride, 300 
iodide, 300 
oxide, 300 
Mercurous chloride, 300 

iodide, 300 
Mercury, 359 

bichloride, 300 
as a caustic, 013 
as a cathartic, 513 
as a diuretic, 530 
as a germicide, 054 
hiniodide, 300 
hypodermic use of, 

309 
with chalk, 300 
Mel a-arsenic-anilid, 359 
Metacresol, 078 
Metallic salts as disinfec- 
tants, 054 
Metha;moglobin, 101, 542 
Methods of administer- 
ing drugs, 4 
Methyl alcohol, 208 

propyl-carbinol-ure-, 

thane, 90 
pyrocatechin, 070 
salicylas, 440 
salicylate, 445 
Methylene blue, 437 
Met hylic alcohol, 208 
Methyloxymethyl salicy- 
late, 450 
Mclhylthionine hydro- 
chloride, 437 



770 



GENERAL INDKX 



Methylthioninae hydro- 

chloridum, 437 
Methylxanthine, 531 
Methysticin, 555 
Metric system, 706 
Mezereon, 397 

ointment, 397 
Mezereum, 397 
Microscopic detection of 

mercury, (note) 362 
Mild mercurous chloride, 

360 
Milk of asafetida, 16 

punch, 207 

sugar, 544 
Mineral acids, 329 

astringents, 291 
Mistura camphors acida, 

332 
Mistura cretee, 636 

ferri composita, 324 

glycyrrhizae compos- 
ita, 619 

rhei et sodae, 504 
Misturae, 2 
Mixture of asafetida, 16 

of rhubarb and soda, 
504 
Mixtures, 2 
Moist heat as a germicide, 

653 
Molasses, 502 
Monkshood, 266 
Monobromated camphor, 

161 
Monohydrated sodium 

carbonate, 632 
Monsel's solution, 327 
Morphina, 58 
Morphinae acetas, 58 

hydrochloridum, 5S 

sulphas, 58 
Morphine, 58 

acetate, 58 

benzyl-ester-hydro- 
chloride, 73 

derivatives, 73 

diacetic ester, 74 

ethyl ester, 73 

habit, 71 

hydrochloride, 58 

sulphate, 58 
Moschus, 14 

moschiferus, 14 
Mucilage of gum arabic, 
618 

of sassafras pith, 619 

of elm bark, 618 

of tragacanth, 618 
Mucilago acacia?, 618 

sassafras medullas, 
619 

tragacanthae, 618 

ulmi, 618 
Mulled wine, 207 
Musk, 14 



Musk-root, 17 

Mustard, 607 

Mustard as an emetic, 496 

flour, 496 

leaves, 607 

plaster, 607 
Mutton suet, 622 
Myristica, 481 

fragrans, 481 

Napelline, 267 
Naphtalinum, 679 
Naphtalin, 679 
Naphthalol, 681 
Naphtol, 680 
Narceine, 72 
Narcotine, 72 
Nataloin, 505 
Nativelle's digitalin, 218 
Nauseating expectorants, 

573 
Nervines, 14 
Neural anaesthesia, 55 
Ngai camphor, (note) 187 
Nicotine, 174 
Nitre, 539 
Nitric acid, 331 

as a caustic, 615 
poison, 329 
Nitrite-oxyhaemoglobin, 

161 
Nitrites, 161 
Nitrogen monoxide, 22 
Nitroglycerin, 161 
Nitro-hydrochloric acid, 

332 

poison, 329 
Nitrous acid, 161, 332 

oxide, 22 
Normal salt solution, 526 
Norway spruce, 610 
Nosophen, 387 
Nucleic acid, 402 
Nucleins, 402 
Nutgall, 287 
Nutmeg, 481 
Nutriants, 283 
Nux vomica, 131 

Oak, 289 

Oatmeal, 502 

Oil of absinthe, 690 
of allspice, 480 
of anise, 480 
of aspic, (note) 475 
of birch, 480 
of bitter almonds, 282 
of cajuput, 440 
of camphor, 192 
of chenopodium, 643 
of cinnamon, 481, 690 
of cloves, 481, 690 
of copaiba, 552 
of cotton seed, 622 
of cubeb, 553 
of erigeron, 555 



Oil of eucalyptus, 440 
of fennel, 480 
of gaultheria, 446, 

480 
of geranium, 690 
of hedeoma, 580 
of juniper, 554 
of lavender, 480 
of lemon, 480 
of linseed, 622 
of marjoram, (note) 

475 
of mentha pulegium, 

580 
of mustard, 607 
of myristica, 480 
of nutmeg, 481 
of orange peel, 480 
of pennyroyal, 580 
of peppermint, 480 
of camphor, 681 
of pimenta, 480 
of rosemary, (note) 

475, 480 
of rue, 579 
of sandal-wood, 555 

690 
of sassafras, 480 
of savine, 579 
of spearmint, 480 
of sweet almonds, 622 
of sweet birch, 446 
of tansy, 580 
of tar, 575 
of theobroma, 623 
of thyme, 682, 690 
of turpentine, 548 
as an anthelmin- 
tic, 646 
of vitriol, 330 
of wine, heavy, (note) 

26 
of wintergreen, 446 
of wormseed, 690 
of zedoary, 690 
Oils, 622 

Ointment of ammonia ted 
mercury, 361 

of chrysarobin, 601 

of galls 288 

of iodine, 374 

of iodoform, 381 

of mercuric nitrate 

361 
of mercury, 360 
of nutgall, 288 
of phenol, 664 
of potassium iodide. 

374 
of red mercuric ox- 
ide, 361 
of rose-water, 622 
of stramonium, 95 
of tannic acid, 285 
of tar, 576 
of veratrine, 266 



GENERAL INDEX 



I 



oil of white precipitate. 
361 
«'i yellow mercuric 

oxide, 361 
of zinc oxide, 108 
no Btearate, 308 
Ointments, :; 
Oleata, 3 
Oleate of atropine. 95 

• ume, 1 Is 

of mercury, :;t;i 
of veratrum, 266 

Oleatea, 3 

Oleatum atropine, !»."> 
coos, I 1 8 
hydrargyri, .'{(i| 

veratri, 266 

(Heir acid, 520 

Oleoreain of capsicum, is.; 
of oubeb, 553 

of fern, 64 I 
of ginger, 482 
of lupulin, is 
of pepper 

Oleoresina aspidii, til I 
cansici, 483 

cuoebffi, 

lupulina-. is 

piperis, 4S3 

zingiberis, ls_> 
Oleoresins, 2 
Oleum adipis, 022 

nthereum, (note) 26 

amygdala? amara?, 282 

amygdala-, cxpres- 
suin, 622 

anisi, 480 

aurantii corticis, 480 

betula?, 446, 480 

cajuputi, 440 

caryophylli, 480 

chenopodii, 643 

cinnamomi. 480 

copaiba?, 552 

cubeba?, 553 

erigerontis, 555 

eucalypti, 440 

gaultheria?, 446, 480 

gossypii seminis, 622 

hedeoma?, 580 

i'uniperi, 554 
ivanduhr, 480 
lini, 1122 
limonis, 480 
mentha? piperita?, 480 
mentlur viritis, 180 
morrlnue, 3SS 
mvristica?, 481 
oliva-, 022 
picis liquida?, 576 
pimenta?, 480 
ricini, 622, 521 
rosmarini, 480 
sabina?, 579 
. santali, 555 
sassafras, 480 



oleum sinapis volatile, 607 

teivl. milium-, .Ms 

terebinthina rectifi- 

caluin, .") is 

theobromatis, 622 
tiglii, 522 

Olive oil, 622 

t taaye poison. 237 
t Ipii pulvis, ">s 

t 'pinanine, 57 
( >pium, ."i7 

deodoratum, 58 
deodorised, 58 
habit, 71 
poisoning by, 67 
smoking, 7 i 
Opsonins, 114 

i irexse bydrochloras, 478 
Orexin, 178 

iaunalc, 178 

Orthocresol, 678 
Orthocresotic acid, (note) 

I.-,.-, 
Orthol'orm, 52 
Orl hoguaiaool-sulphonic 

acid, 678 
Orthophosphoric acid, 334 
Oxalic acid, 685 

poisoning, 6S5 
( >xgall, 508 

' U&ldjzing disinfectants, 

en 

Oxyeamphor, 192 
Oxycannabin, 1 14 

Oxydicolchieine, 391 

( Kvsparteine, (note) 248 

Oxytocics, 582 

Pahouius poison, 237 
Pancreatin, 648 
Pancreatized foods, 648 
Papain, 651 

Papaver somniferum, 57 
Papaverine, 72 
Papaw, 651 
Papayotin 651 
Paracetamidophenol, 

(note) 466 
Paracresol, 678 
Paracresotic acid, (note) 

455 
Paraffin, 623 
Paraffinum, 622 
Paraform, 688 
Paraformaldehyde, 687 
Paraldehyde, 87 
Paraldehydum, 87 
Paramidophenol, (note) 

466 
Paramorphine, 57 
Paraxanthin, 532 
Paregoric, 58 
Pareira, 547 

brava, 547 
Parillin, 396 
Parsley, 580 



Paullinia oampana, 209 
Pearl barlej . 620 
Pelletierinsa tannas, 646 
I'ellei ierine, tilt; 
Pennyroyal, 580 
Pental, 37 
Pepo, 645 
Pepper, 182 
Peppermint, 180 

water, 480 

Papain, 8 18 
Pepsinum, 6 I s ; 
Peptonized beef tea, 650 
gruel, tii<» 

milk, til'.) 

Pernambuoo jaborandi. 

562 
Peronine, 73 

Peroxide of hydrogen, titii 
Peruvian baric, I L9 

coca, 117 
l'cst serum, 112 

Petrolatum, 623 

album, 622 
liquidum, (122 
Pharmacodynamics, 1 
l'harmacology, 1 
Pliarmacopceia, 1 
Pharmacy, 1 
Phellandrene, 440 
Phcnaeetin, 470 
Phenazonum, 457 
Phenocoll hydrochloride, 

471 
Phenol, 664 

liquefactum, 664 
poisoning, 670 
sodique, 703 
Phenolplithalein, 507 
Phenolsulphonic acid, 673 
Phenyl salicylate, 446 
Phenylacetamide, 466 
Phenyldihydrochinazo- 
Iine hydrochlorate, 
478 
Phenyl-dimethyl-pyrazo- 

lone, 457 
Phenylic alcohol, 664 
Phenylis salicylas, 446 
Phosphoric acid, 334 
Phosphorus, 338 
necrosis, 345 
poisoning, 340 
sesquisulphide, (note) 
345 
Phosphoryl quinine, 436 
Physiological salt, solu- 
tion, 526 
Physostigma, 145 
poisoning, 152 
venenosum, 145 
Physostigmina? salicylas, 
146 
sulphas, 146 
Physostigmine, 145 
salicylate, 146 



772 



GENERAL INDEX 



Physostigmine sulphate. 

146 
Picraconitine, 267 
Picrasma excelsa, 476 
Picric acid, 647 
Picrasmin, 476 
Pieropodophyllin, (note) 

517 
Pill of aloes, 505 

of aloes and iron, 505 
of aloes and mastic, 

505 
of aloes and myrrh, 

505 
of asafetida, 16 
of ferrous carbonate, 

323 
of opium, 58 
of phosphorus, 338 
of podophyllum, cap- 
sicum, and bella- 
donna, 518 
Pills, 3 

Pilocarpidine, (note) 563 
Pilocarpine hydrochlor- 
idum, 563 
nitras, 563 
Pilocarpine, 563 

hydrochloride, 563 
nitrate, 563 
Pilocarpus, 562 
jaborandi, 563 
microphyllus, 563 
pinnatus, (note) 562 
Pilulae, 3 

aloes, 505 

aloes et asafcetidae, 

505 
aloes et ferri, 505 
aloes et mastiches, 

505 
aloes et myrrhae, 505 
asafcetidae, 16 
catharticae compos- 

itae, 361, 517 
catharticae vegeta- 
bles, 517 
ferri carbonas, 323 
laxativae compositae, 

505 
opii, 58 
Pilulae phosphori, 338 

podophylli, capsici et 

belladonnas, 518 
rhei compositae, 504 
Pimenta, 482 

officinalis, 482 
Pinkroot, 642 
Pinus palustris, 548 
Pipe gamboge, 520 
Piper, 483 

angustifolium, 554 
cubeba, 553 
methysticum, 555 
nigrum, 482 
Piperazidine, 543 



Pipcrazine, 543 

hydrochloride, 543 
Piperine, 482 
Piperin, 483 
Pipsissewa, 547 
Pitch, 575 
Pituitary body, 406 
Pix burgundiea, 610 

liquida, 575 
Plasma of starch, 622 
Plaster of belladonna, 95 

of mercury, 361 

of paris, 636 
Plasters, 3 

Piatt's chlorides, 703 
Plumbi acetas, 293 

carbonas, 293 

nitras, 293 

oxidum, 293 
Plumbism, 295 
Plumbum, 293 
Podophyllin, 518 
Podophyllinic acid, (note) 

518 
Podophylloresin, 518 
Podophyllotoxin, 518 
Podophyllum, 517 

peltatum, 517 
Polygala senega, 574 
Polymerized formalde- 
hyde, (note) 689 
Polystichic acid, (note) 

643 
Pomegranate rind, 646 
Poppy, 57 
Porcelain clay, 627 
Porphyroxine, 72 
Potash, 535 

Potassa sulphurata, 658 
Potassii acetas, 535 

bicarbonas, 535 

bitartras, 535 

bromidum, 154 

carbonas, 535 

chloras, 540 

citras, 508 

effervescens, 535 

cyanidum, 276 

et sodii tartras, 508 

hydroxidum, 535 

hypophosphis, 336 

iodidum, 374 

nitras, 539 

permanganas, 660 
Potassium, 534 

acetate, 535 

alum, 291 

and sodium tartrate, 
512 

bicarbonate, 535 

bitartrate, 508, 535 

bromide, 154 

carbonate, 535 

chlorate, 540 

poisoning by, 
541 



Potassium citrate, 508, 
512, 535, 573 
cyanide, 276 
hydroxide, 535 

as a caustic, 612 
hypophosphite, 336 
iodide, 374 
myronate, 607 
nitrate, 539 

poisoning by, 539 
oxalate, 685 
permanganate, 660 
as e m m e n a - 
gogue, 580 
Poudre de succession, 

(note) 294 
Poultices, 628 
Powder of ipecac and 
opium, 58 

of morphine, com- 
pound, 58 
Powdered opium, 58 
Powders, 3 

Practical anaesthesia, 37 
disinfection, 698 
local anaesthesia, 52 
Precipitated calcium car- 
bonate, 636 

calcium phosphate, 

335 
sulphur, 693 
zinc carbonate, 308 
Predigested foods, 649 
Preparations of drugs, 2 
Prepared chalk, 636 
Prescribing, art of, 8 
Prickly pear, 397 
Pride of China, 647 
Propenyl alcohol, 624 
Proprietary disinfectants, 

(note) 658 
Propylamin, 388 
Protargol, 321 
Protiodide of mercury, 

360 
Protoveratrine, 262 
Prunes, 503 
Prunum, 503 
Prunus serotina, 477 

virginiana, 477 
Prussic acid, 275 

poisoning, 280 
Pseudaconitine, (note) 266 
Pseudocannabinol, 114 
Pseudojervine, 262 
Psychotrine, 488 
Pterocarpus marsupium, 

289 
Ptyalism, 362 
Pulveres, 3 

Pulvis aromaticus, 480 
cretae compositus, 636 
effervescens composi- 
tus, 508 
glvcyrrhiza composi- 
tus, 506 



GENERAL 1NDKX 



"W 



Pulvia ipeoaouanhffi et 

«>|>ii, 68, IS' I 

jala pa oompoBil us, 

618 
morphine oomposi 

in,. 
rhei oompositus, 60 1 
Pampkiii Beed, r> i"> 
Punica granatum, 6 16 
Punioine, t> lt> 
Purgatives. 197 

hypodermic use of, 
60] 

Purging agaric, 290 

cassia, 603 
Purified aloes, 606 

animal charcoal, 652 

extract of licorice 
root, 619 

oxgall, .508 
Purshianin, 507 
Pyramiilon, 17- 

bicamphorate, 473 

camphorate, 473 

salicylate, 473 
Pyrocatechin, 683 
Pyrogallic acid, 616 
Pyrogallol, 616 
Pyroligneous acid, 575 
Pyroxylic spirits, 208 
Pyroxylin, 630 

Quassia, 476 

amara, 476 
Quassin, 476 
Quebrachamine, 179 
Quebrachine, 179 
Quebracho, 179 
Queen's root, 397 
Quercus alba, 289 

infectoria, 287 
Quevenne's iron, 448 
Quillaja, 574 
Quillaja soponaria, 574 
Quinic ester of quinine, 

437 
Quinidinse sulphas, 419 
Quinidine, 419 
Quinina, 419 
Quininae bisulphas, 420 

hydrobromidum, 120 

hydrocliloridum, 420 

sulphas, 419 
Quinine, 419 

bisulphate, 420 

dihydroxyl, (note) 421 

esters, 436 

hydrobromide, 420 

hydrochloride, 420 

poisoning, 433 

salicylate, 420 

sulphate, 420 

Rectified oil of turpen- 
tine, 548 
Red cinchona, 419 



Red gum, l io 

mercuric iodide, 860 
mercuric oxide, 860 

rose, 289 

wine, L92 
Reduced iron, 
Refie* emetics, 196 
Relation of apothecaries' 

to metric weights, 707 
of apothecaries' 
weights to meas- 
ures, 707 
of metric to apothe- 
caries' weights, 708 

Rennet, 648 

Resin cerate, 548 
of jalap, 516 
of May-apple, 518 
of podophyllum, .">1X 
of scammony, 517 

Itesina, 548 
jalaps, 516 
podophylli, 518 
scammonii, 517 

Resinous cathartics, 515 

Resins, 2 

Resorcin, 683 

Resorcinol, 683 

Rhamnus, 507 
frangula, 507 
purshiana, 507 

Rhatany, 288 

Rheum, 503 

officinale, 503 

Rhodalline, 398 

Rhubarb, 503 

Rhus glabra, 288 

Ricin, 521 

Ricinoleic acid, 521 

Ricinolein, 521 

Ricinus communis, 521 

Rio Janeiro jaborandi, 562 

Rochelle salt, 508 

Roman chamomile, 483 

Rosa gallica, 289 

Rose leaves, 289 

Rosemary, oil of, (note) 
475 

Rosin, 548 

Roth-Drager inhaler, 
(note) 44 

Rottlerin, 647 

Rubefacients, 607 

Rubijervine, 262 

Rubaronic acid, 472 

Rue, 579 

Russian bath, 559 

Ruta graveolens, 579 

Sabadilline, (note) 266 
Sabina, 579 

Saccharated ferrous car- 
bonate, 323 
Saccharin, 627 
iSaccharum, 502, 544 
lactis, 502, 544 



Saigon cinnamon. 181 

mmoniac, 183 
Salioin, 1 16 

Salioj la be of , l«na phi "I 
ether, 681 

Salicylic acid, I 16 

acid poisoning, 464 

amj Ic -ill, i.. i. 

esters, 166 

met li\ low iiicl hyl- 

ester, 166 

Salicyluric acid, I Hi 

Saligenin, l li> 
Saline cathartics, .Mis 

diuretics, 533 
Saliyprin. 472 
Salol, 446 
Salophen, 457 
Saloiiuinine, 437 
Balseparin, 397 
Salt action, 534 

of sorrel, 685 
Sanguinaria, 577 
Sanguinarine, 577 
Santalum album, 555 
Santogenin, 640 
Santonica, 639 
Santonin, 639 
Santoninic acid, 639 
Santoninum, 640 
Sapo, 600 

mollis, 600 
Saponin, 396, 574 
Sarillinic acid, 397 
Sarsaparilla, 396 
Sarsaparillin, 397 
Sarsaponin, 396 
Sassafras, oil of, 480 

pith, 619 
Saturnine cerebritis, 297 
Saturnism, 296 
Savine, 579 
Scammonin, 517 
Scammonium, 517 
Scammony, 517 
Scheele's green, 358 
Schleich's intiltration-an- 

ffisthesia, 52 
Schweinfurt green, 358 
Scilla, 528 
Scillin, 528 
Scillipicrin, 528 
SciUitin, 528 
Scillitoxin, 528 
Scoparin, 530 
Scoparius, 529 
Scopola, 95 

carniolica, 95 

japonica, 95 
Scopolamine, 108 

hydrobromide, 109 

-morphine anaesthe- 
sia, 1 1 1 
Secale cereale, 582 
Seidlitz powder, 508 
Senega, 574 



774 



GENERAL INDEX 



Senna, 506 

Serpentaria, 484 

Serum antidiphthericum, 

408 
Sevum, 622 

Sex in relation to dose, 7 
Shore oil, 388 
Silberol, 319 
Silver, 312 

acetate, 319 

as a germicide, 655 

caseinate, 320 

citrate, 319 

cyanide, 312 

fluoride, 659 

lactate, 319 

nitrate, 313 

nitrate, diluted, 313 

nitrate, fused, 313 

oxide, 313 

poisoning, 317 

soluble, 320 

sulphocarbolate, 319 

thiosulphonate, 320 

vitellin, 319 
Simple bitters, 476 
Sinalbin, 607 
Sinapis alba, 607 

nigra, 607 
Sinigrin, 607 
Slippery elm, 618 

poultice, 618 
Smilacin, 397 
Smilax, 396 

Snake-poisoning antitox- 
in, 413 
Soap, 600 

liniment, 187 

plaster, 293 
Soap-bark, 574 
Socaloin, 505 
Socotrine, aloes, 504 
Soda, 632 
Sodii arsenas, 346 

arsenas exsiccatus, 
346 

benzoas, 691 

bicarbonas, 632 

bisulphis, 694 

boras, 695 

bromidum, 154 

carbonas monohy- 
dras, 632 

hydroxidum, 632 

hypophosphis, 336 

iodidum, 374 

nitris, 162 

phenolsulphonas, 673 

phosphas, 334, 508 

phosphas efferves- 
cens, 508 

phasplias exsiccatus, 
508 

salicylas, 446 

sulphas, 508 

sulphis, 694 



Sodium, 632 

and caffeine benzo- 
ate, 217 

and theobromine sal- 
icylate, 531 

arsenate, 346 

benzoate, 691 

bicarbonate, 632 

bisulphite, 694 

borate, 695 

bromide, 154 

cacodylate, 359 

carbonate, 632 

chlorate, (note) 541 

cinnamate, 693 

fluoride, 659 

hydroxide, 632 

hypochlorite, 826 

hypophosphite, 336 

iodide, 374 

nitrite, 162 

phenolsulphonate, 
673 

phosphate, 334, 510 

salicylate, 446 

santoninate, 642 

sulphate, 510 

sulphite, 694 

sulphocarbolate, 673 

theobromine salicy- 
late, 531 

Soft soap, 600 
Solid extracts, 3 
Soluble ferric phosphate, 
323 

ferric pyrophosphate, 
323 

iron and quinine cit- 
rate, 323 

silver, 320 
Solution of arsenic and 
mercuric iodide, 346, 
371 

of arsenous acid, 346 

of caustic potash, 535 

of chlorinated soda, 
656 

of ferric subsulphate, 
327 

of ferric sulphate, 324 

of formaldehyde, 686 

of gutta-percha, 630 

of hydrogen dioxide, 
661 

of lead subacetate, 
293 

of lime, 636 

of magnesium citrate, 
512 

of mercuric nitrate, 
614 

of persulphate of iron, 
324 

of potassa, 535 

of potassium arsen- 
ite, 346 



Solution of potassium cit- 
rate, 512, 535 

of sodium arsenate, 

346 
of sodium hydroxide, 

632 
of subsulphate of 

iron, 327 
of zinc chloride, 308 

Solutions, 2 

Somnifacients, 57 

Soziodol, 387 

Spanish flies, 604 

Sparteinae sulphas, 248 

Sparteine, 248, 530 

• > sulphate, 248 

Spearmint water, 480 

Spermaceti, 622 

Sphacelinic acid, 582 

Sphacelotoxin, 582 

Spice plasters, 608 

Spigelia, 642 

marilandica, 642 

Spigeline, 642 

Spinal anaesthesia, 54 

Spirit of ammonia, 183 
aromatic, 183 
of anise, 480 
of camphor, 187 
of chloroform, 30 
of cinnamon, 480 
of ether, 26 
of ether, compound, 

26 
of gaultheria, 480 
of glonoin, 162 
of glyceryl nitrate 

162 
of juniper, 554 
of lavender, 480 
of nitrous ether, 162 
of peppermint, 480 
of spearmint, 480 

Spirits, 3 

Spiritus, 3 

aetheris, 26 

aetheris compositus, 

26 
aetheris nitrosi, 162 
ammoniae, 183 
ammoniae aromati- 

cus, 183 
anisi, 480 
aurantii compositus, 

480 
camphorae, 187 
chloroformi, 30 
cinnamomi, 480 
frumenti, 192 
gaultheriae, 480 
glycerylis nitratis, 

162 
juniperi, 554 
juniperi compositus, 

554 
lavandulae, 480 





GENEB \l. [NDEX 


77. r , 


Spiritus menthffi piperita, 


Sulphonmethanum, 83 


Syrupus acid] hydriodioi, 


ISO 


Sulphur, 893 




virdis, 180 


Sulphur dioxide, 894 


acidi oil rioi, .>I2 


vini gallici, 192 


lot urn, 693 


althjB®, 020 


Spleen, 107 


precipitatum. 693 


aurantu, 180 


Squill, 528 


Bublimatum, 893 


oalcis. 836 


Squirting cucumber, 518 


Sulphurated lime, 09 1 


l'erri lodidi, 324 


Starch, 619 


Sulphuretted hydrogen, 


I'erri quininse el Btry- 


Stearic acid, 022 


57S 


chinina' phospha- 


Steroulia acuminata, 209 


Sulphuric acid, 330 


tis, 321 


Stillingia, 397 


poisoning, 320 


fuscus, 502 


Stillingine, 307 
Stimulating diuretics. 628 


Sulphuris iodidum, 693 


bypophosphit urn, 336 


Sulphurous acid, 694 


hy pophosph i I u in 


expectorants, 57 I 


Sumach, 288 


compositum, 330 


Stomachics, I7."> 


Sumbul. 17 


ipecacuanha}, 189 


Stovaine. 52 


Sumbuho acid, 17 


krtunerite, 2SS 


Straits ofl, 388 


Suppositoria, 3 


laetucarii, 20 


Si rept ococcus antitoxin, 


Suppositories, 3, 5 


picis liquids, 576 


110 


urethral, 5 


pruni Virginians, I7S 


Stronger water of ammo- 


Suprarenal capsule, 211 


rhei, 504 


nia, [83 


Suprarenin, 212 


rhei aromaticus, 504 


Strontii bromidum, 154 


Surinam quassia, 470 


rosae, 289 


iodidum, 37 I 


Sweet orange peel, 630 


sarsaparillaa compos- 


betas, 545 

salicylas, 440 


spirit of nitre, 685, 


itus, 529 


72S 


scillse, 528 


Strontium, ~>1 1 


tincture of rhubarb, 


scillo2 compositus,257 


bromide, 1.54 


664 


senegas, 574 


iodide, 374 


Swertia chirata, 477 


sennae, 506 


lactate, ■"> 1.") 


Sydenham's laudanum, 58 


tolutanus, 577 


salicylate, 146 


Synthetic oil of cloves, 480 


zingiberis, 628 


Strophanthin, 237 


Syrups, 544 


Systemic lavage, (note! 


Strophanthinum, 237 


Syrup of acacia, 618 


127 


Strophanthus, 237 
hispidus, 237 


of althaea, 620 


Systemic remedies, 14 


of citric acid, 512 




komb£, 237 


of ferrous iodide, 328 


Tabacum, 174 


Strychnic acid, 132 


of hydriodic acid, 374 


Table of apothecaries' 


Btrychnina, 131 


of hvpophosphites, 


weights and measures, 


poisoning, 140 


336 


706 


Strychnine nitras, 131 


of iodide of iron, 324, 


Table of cost of various 


sulphas, 131 


328 


disinfectants, (note) 658 


Strychnine nitrate, 131 


of ipecacuanha, 489 


Table of germicides, 703 


sulphate, 131 


of iron, quinine and 


Table of the proportion 


Strychnos mix vomica, 


strychnine phos- 


of alcohol in different 


131 


phate, 324 
of lcrameria, 288 


wines, 709 


Stupes, 550 


Table of relation of apoth- 


Styptic collodion, 285, 030 


of lactucarium, 20 


ecaries' weights to met- 


Stypticin, 291 


of lime, 636 


rical weights, 707 


Styptics, 284 


of orange, 480 


Table of relation of apoth- 


Styrax benzoin, 690 


of rhubarb, 504 


ecaries' weights and 


Subacute lead-poisoning, 


of rose, 289 


measures to each other, 


296 


of sarsaparilla, com- 


707 


Subcutaneous injections, 4 


pound, 257 


Table of weights and 


Sublimed sulphur, 693 


of senega, 739 


measures of the metri- 


Succus limonis, 480 


of senna, 506 


cal system, 706 


Suet, 622 


of squill, 528 


Tachiol, 659 


Sugar, 502 


of squill, compound, 


Tamarind, 503 


as a diuretic, 544 


528, 257 


Tamarindus, 503 


of lead, 293 


of sweet orange peel, 


Tanacetum, 580 


of milk, 502 


480 


vulgare, 580 


Sulphites, 695 


of tar, 576 


Tannacol, 289 


Sulpho-carbolic acid, 673 


of Tolu, 577 


Tannalbin, 289 


Sulphonal, 83 


of wild cherry, 478 


Tannate of cannabene, 117 


poisoning, 85 
Sul phones, 83 


Syrupi, 2 


Tannic acid, 284 


Syrups, 2 


compounds, 289 
Tannin albuminate, 289 


Sul phone thylmethanum, 


Syrupus, 544 


83 


acaciae, 618 


Tannoform, 289 



776 



GENERAL INDEX 



Tannopine, 289 
Tannon, 289 
Tansy, 580 
Tar, 575 

Tar camphor, 679 
Taraxacum, 397 

officinale, 397 
Tartar, 511 

emetic, 257 
poisoning, 260 
Tartaric acid, 511 
Tea, 209 
Temperament in relation 

to dose, 6 
Terebene, 575 
Terebenum, 575 
Terebinthina, 548 

canadensis, 548 
Terpin hydrate, 575 
Terpini hydras, 575 
Tertiary amyl nitrite, 

(note) 161 
Tetano-cannabene, 114 
Tetanus antitoxin, 410 
Tetra-iodo-phenol-phtha- 

lein, 387 
Tetra-iodopyrrol, 386 
Tetra-methylthionine hy- 
drochloride, 580 
Thea sinensis, 209 
Thebaine, 72 
Thebolactic acid, 57 
Theine, 209 
Theobromine, 531 

and sodium salicy- 
late, 531 

and sodium acetate, 
532 
Theocin, 532 
Theocol, 678 
TheophyUin, 532 
Thermol, 618 
Thiosinamine, 398 
Thymol as anthelmintic, 
646 

as a disinfectant, 
682 
Thymolis iodidum, 386 

682 
Thymus serpyllum, (note) 
682 

vulgaris, 682 
Thyreoantitoxin, 403 
Thyroid body, 403 
Thyroidismus, 536 
Thyroiodin, 403 
Time for administration 

of drugs, 7 
Tinctura aconiti, 267 

aloes, 505 

aloes et myrrhse, 505 

antiperiodica, (note) 
436 

arnica?, 610 

asafcetidae, 16 

aurantii dulcis, 480 



Tinctura belladonna 1 foli- 
orum, 95 

benzoini, 691 

benzoini composita, 
691 

calumbae, 477 

cannabis indicae, 114 

cantharidis, 605 

cardamomi, 480 

cardamomi compos- 
ita, 480 

cimicifugae, 18 

cinchonas, 419 

cinchonas composita, 
419 

cinnamomi, 480 

colchici seminis, 391 

digitalis, 218 

ferri chloridi, 324 

gallae, 288 

gambir composita, 
288 

gelsemii, 172 

gentianae composita, 
477 

guaiaci, 397 

guaiaci ammoniata, 
397 

hydrastis, 592 

hyoscyami, 95 

iodi, 374 

ipecacuanhas, et opii 
58, 489 

kino, 288 

krameriae, 288 

lavandulae composi- 
te, 480 

lactucarii, 20 

limonis corticis, 480 

lobeliae, 171 

moschi, 14 

nucis vomicae, 131 

opii, 58 

opii camphorata, 58 

opii deodorati, 58 

physostigmatis, 146 

quassiae, 476 

rhei, 504 

rhei aromatica, 504 

scillae, 528 

serpentariae, 484 

stramonii, 95 

strophanthi, 237 

tolutana, 577 

Valerianae, 15 

Valerianae ammoni- 
ata, 15 

veratri, 263 

zingiberis, 482 
Tincturae, 3 
Tincture of aconite, 267 

of aloes, 505 

of aloes and myrrh, 
505 

of arnica, 610 

of asafetida, 16 



Tincture of belladonna 
leaves, 95 

of benzoin, 691 

of cannabis indica, 

114 
of cantharides, 605 
of cardamom, 480 
of chloride of iron, 

324, 328 
of cimicifuga, 18 
of cinchona, 419 
of cinnamon, 480 
of colchicum seeds, 

391 
of Colombo, 477 
of digitalis, 218 
of ferric chloride, 

324 
of galls, 288 
of gambir, 288 
of gelsemium, 172 
of gentian compound, 

477 
of ginger, 482 
of guaiac, 397 
of guaiac, ammonia- 
ted, 397 
of hemp, 114 
of hydrastis, 592 
of hyoscyamus, 95 
of Indian cannabis, 

58 
of iodine, 374 
of ipecac and opium, 

141 
of kino, 288 
of krameria, 288 
of lactucarium, 20 
of lemon peel, 480 
of lobelia, 171 
of musk, 14 
of nutgall, 288 
of nux vomica, 131 
of opium, 58 
of opium, camphor- 
ated, 58 
of opium, deodorized, 

58 
of physostigma, 146 
of quassia, 476 
of rhatany, 288 
of rhubarb, 504 
of serpentaria, 484 
of squill, 528 
of stramonium, 95 
of strophanthus, 237 
of sweet orange peel, 

480 
of Tolu, 577 
of valerian, 15 
of valerian, ammoni- 

ated, 15 
of veratrum, 263 
Tinctures, 3 
Tinnevelly senna, 506 
Tobacco, 174 



GENERAL INDEX 



Toluifera balsamum, 577 
pereirm, 577 

Tonics, 323 

Toxins and antitoxins, 107 

Tragacanth, 618 

Tragacanl ha , 618 

Tricolor terl lary butyl al- 
cohol, 91 

Tribasio pyrophosphoric 
acid, (note) 38 1 

Trichloraldehyde, 75 

Trichlormethane, 30 

Trichloracel ic acid, 61S 

Trichlorisopropyl alcohol, 

Trimethylethylene, :>7 
Trimethylxanthin, 210 
Trinitro-cellulose, 630 
Trional, 83 
Trioxymel hylanthraqui- 

aone, 503 
Triple elixir. 324 
Triticum, 548 
Triturate of elaterin, 519 
Trituratio elaterini, 519 
Troches, 3 

of gambir, 288 

of licorice and opium, 
619 

of krameria, 288 

of potassium chlo- 
rate, 540 

of santonin, 640 

of tannic acid, 285 
Trochisci, 3 

acidi tannici, 285 

gainbir, 288 

glycyrrhizffi et opii, 
619 

kramerise, 288 

potassii chloratis, 5 10 

santonini, 640 
Tropacocaine, 51 
True chamomile, 4S3 
liuxillo, 117 
Tuberculin, 415 
Tully's powder, 58 
Turkish bath, 559 
Turpentine, 548 

as an anthelmintic, 
646 

enema ta. 550 

liniment , 548 

st u pes, 550 
Turpeth mineral, 371 

Ulmus, 618 
fulva, 618 

Unbolted flour, .502 

Unguent a, 3 

Unguentum, 622 

acidi tannici, 285 
aqua rosse, 622 
chrysarobin, 601 
galke, 288 
hydrargyri, 360 



l aguent am hydrargyi i 
ammonia! i, 360 
hydrargyri nitral is. 

361 
hydrargyri oxidi 11a- 
' vi. :;tii 

oxidi rubri, 361 

iodi, 37 I 
iodoform!, 381 
phenolis, 66 I 
picis liquids. 576 
potassii iodiai, 37 I 
stramonii, 95 
Bulphuris, 693 
veratrinffi, 266 

zinci oxidi, 308 

rinci stearatis, 308 
Unslaked lime, 635 
l rethane, 89 

I retinal suppositories, 5 
Urginea mantima, 528 
Urochloralic acid, 76 
(Jrohsematoporphyrine, 

299 
[Jrotropin, 556 
Uva ursi, 5 Mi 

Valerian, 15 

Valeriana officinalis, 15 
Valeric acid, 15 
Vallet's mass, 323 
Vapor bath, 559 
Vaseline, 623 
Vegetable astringents, 284 

cathartic pills, 517 
Veratrina, 266 
Veratrine, 266 

ointment, 266 
Veratrum, 262 

album, 262 

sebadilla, 266 

viride, 202 

viride, poisoning by, 
265 
Vermicides, 639 
Vermifuges, 639 
Veronal, 91 

Veronica virginica, 520 
Vesicatories, 604 
Viburnum opulus, 581 

prunifolium, 581 
Vienna paste, 612 
Vina, 3 
Vinegar of opium, 58 

of squill, 528 
Vinegars, 3 
Vinum album, 192 

antimonii, 257 

coca?, 118 

colchici seminis, 391 

ergotse, 583 

ferri, 324 

ferri amarum, 324 

ipecacuanha?, 489 

opii, 58 

rubrum, 102 



Virginia snake root , I s I 
\ olal tie oil <>i mustard, 
607 

oils, 2, 175 
oils as <ii linfectants, 
690 

Wahoo, 520 

\\ mi burg's tinct ure, 436 
Warming plaster, two 
Washed sulphur, 693 
Washing sooa. 632 
Water as a diuretic. 525 

Of ammonia, 183 

of chloroform, 30 
of creosote, (>7l 
of hamamelis, 289 

Waters, 2 
Wax, 022 

Weights and measures, 

701) 
West India pepper, 483 
Whiskey, 192 
\\ bite agaric, 290 

arsenic, 346 

bees-wax, 622 

ginger, 482 

mustard, G07 

oak, 289 

pepper, 482 

sugar, 502 

turpentine, 548 

vitriol, 308 

wax, 622 

wine, 192 
Wild cherry, 477 
Wine, 192 
Wine of antimony, 257 

of coca, 118 

of colchicum seed, 
391 

of ergot, 583 

of ipecacuanha, 489 

of opium, 58 

whey, 206 
Wines, 3 
Witch-hazel, 289 
Wood alcohol, 208 
Wool fat, 623 

Xanthin compounds, 531 
Xanthopuccine, 592 
Xanthoxylum, 397 
Xylic acid, 664 

Yaupon, 209 

Yellow bees-wax, 622 

gentian, 476 

jessamine, 172 

mercuric oxide, 360 

mercuric subsul- 
phate, 371 

mercurous iodide, 360 

prussiate of potash, 
311 

wash, 371 



778 



GENERAL INDEX 






Yellow wax, 622 
Yohimbine, 556 
Young's rule for doses, 7 

Zinc, 307 

acetate, 309 
bromide, 309 
carbonate, 309 
chloride, 309 

as a caustic, 613 
as a disinfect - 
ant, 656 



Zinc iodide, 309 
oxide, 308 
phenolsulphonate, 

309, 673 
phosphide, 346 
stearate, 309 
sulphate, 308, 496, 656 
sulphocarbolate, 309 

673 
valerate, 308 

Zinci acetas, 308 



Zinci bromidum, 308 

carbonas precipita- 
tus, 308 

chloridum, 308 

iodidum, 308 

oxidum, 308 

phenolsulphonas, 308 
673 

stearas, 308 

valeras, 308 
Zingiber, 482 

officinale, 482 



THE END 



